CA1084498A - Benzylpyrimidines and process for the preparation thereof - Google Patents
Benzylpyrimidines and process for the preparation thereofInfo
- Publication number
- CA1084498A CA1084498A CA301,705A CA301705A CA1084498A CA 1084498 A CA1084498 A CA 1084498A CA 301705 A CA301705 A CA 301705A CA 1084498 A CA1084498 A CA 1084498A
- Authority
- CA
- Canada
- Prior art keywords
- group
- represent
- formula
- compound
- benzylpyrimidines
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 238000000034 method Methods 0.000 title claims abstract description 30
- OOLOAWZLPBDRJQ-UHFFFAOYSA-N 2-benzylpyrimidine Chemical class N=1C=CC=NC=1CC1=CC=CC=C1 OOLOAWZLPBDRJQ-UHFFFAOYSA-N 0.000 title claims abstract description 19
- 238000002360 preparation method Methods 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 38
- 239000002253 acid Substances 0.000 claims abstract description 21
- 150000003839 salts Chemical class 0.000 claims abstract description 13
- 238000004519 manufacturing process Methods 0.000 claims abstract description 6
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims abstract description 4
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract 7
- 239000007858 starting material Substances 0.000 claims description 15
- KRRCOZZNVSJYJA-UHFFFAOYSA-N 5-[(3,5-dimethoxy-4-prop-1-en-2-ylphenyl)methyl]pyrimidine-2,4-diamine Chemical compound COC1=C(C(C)=C)C(OC)=CC(CC=2C(=NC(N)=NC=2)N)=C1 KRRCOZZNVSJYJA-UHFFFAOYSA-N 0.000 claims description 13
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
- 239000000460 chlorine Substances 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 7
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 6
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 6
- 125000006239 protecting group Chemical group 0.000 claims description 6
- 150000002357 guanidines Chemical class 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 238000003776 cleavage reaction Methods 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 230000007017 scission Effects 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 3
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 2
- 230000001580 bacterial effect Effects 0.000 abstract description 4
- 230000000694 effects Effects 0.000 abstract description 3
- 150000003456 sulfonamides Chemical class 0.000 abstract description 3
- 102000003960 Ligases Human genes 0.000 abstract description 2
- 108090000364 Ligases Proteins 0.000 abstract description 2
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 2
- 239000003112 inhibitor Substances 0.000 abstract description 2
- 230000003389 potentiating effect Effects 0.000 abstract description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 63
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 35
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 32
- 239000000243 solution Substances 0.000 description 27
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 26
- 238000002844 melting Methods 0.000 description 25
- 230000008018 melting Effects 0.000 description 25
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 23
- 239000000203 mixture Substances 0.000 description 23
- 239000000725 suspension Substances 0.000 description 19
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
- 238000010992 reflux Methods 0.000 description 17
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- 238000003756 stirring Methods 0.000 description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 235000011167 hydrochloric acid Nutrition 0.000 description 11
- 229960000443 hydrochloric acid Drugs 0.000 description 11
- -1 15 - propyl Chemical group 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 8
- 238000001816 cooling Methods 0.000 description 8
- 239000000825 pharmaceutical preparation Substances 0.000 description 8
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 7
- 238000001953 recrystallisation Methods 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
- 235000011114 ammonium hydroxide Nutrition 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 6
- NTDRVOIFYJNLGZ-UHFFFAOYSA-N 3,5-dimethoxy-4-prop-1-en-2-ylbenzaldehyde Chemical compound COC1=CC(C=O)=CC(OC)=C1C(C)=C NTDRVOIFYJNLGZ-UHFFFAOYSA-N 0.000 description 5
- 229960000583 acetic acid Drugs 0.000 description 5
- 230000018044 dehydration Effects 0.000 description 5
- 238000006297 dehydration reaction Methods 0.000 description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 241000588724 Escherichia coli Species 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 125000003277 amino group Chemical group 0.000 description 4
- STIAPHVBRDNOAJ-UHFFFAOYSA-N carbamimidoylazanium;carbonate Chemical compound NC(N)=N.NC(N)=N.OC(O)=O STIAPHVBRDNOAJ-UHFFFAOYSA-N 0.000 description 4
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 4
- 229960004198 guanidine Drugs 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 150000002825 nitriles Chemical class 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- ZFVAFHCVHOZEBX-UHFFFAOYSA-N 5-[(3,5-diethoxy-4-prop-1-en-2-ylphenyl)methyl]pyrimidine-2,4-diamine Chemical compound CCOC1=C(C(C)=C)C(OCC)=CC(CC=2C(=NC(N)=NC=2)N)=C1 ZFVAFHCVHOZEBX-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
- 235000011054 acetic acid Nutrition 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- 239000004310 lactic acid Substances 0.000 description 3
- 235000014655 lactic acid Nutrition 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 239000012279 sodium borohydride Substances 0.000 description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 description 3
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 2
- MSLZPCFLGWAVNU-UHFFFAOYSA-N 3,5-diethoxy-4-prop-1-en-2-ylbenzaldehyde Chemical compound CCOC1=CC(C=O)=CC(OCC)=C1C(C)=C MSLZPCFLGWAVNU-UHFFFAOYSA-N 0.000 description 2
- JOOXCMJARBKPKM-UHFFFAOYSA-N 4-oxopentanoic acid Chemical compound CC(=O)CCC(O)=O JOOXCMJARBKPKM-UHFFFAOYSA-N 0.000 description 2
- MVSUQKDBQBKQKY-UHFFFAOYSA-N 5-[(2,4-diaminopyrimidin-5-yl)methyl]-3-methoxy-2-prop-1-en-2-ylphenol Chemical compound OC1=C(C(C)=C)C(OC)=CC(CC=2C(=NC(N)=NC=2)N)=C1 MVSUQKDBQBKQKY-UHFFFAOYSA-N 0.000 description 2
- GMZHQBQZNKIIIQ-UHFFFAOYSA-N 5-[(3-ethoxy-5-methoxy-4-prop-1-en-2-ylphenyl)methyl]pyrimidine-2,4-diamine Chemical compound COC1=C(C(C)=C)C(OCC)=CC(CC=2C(=NC(N)=NC=2)N)=C1 GMZHQBQZNKIIIQ-UHFFFAOYSA-N 0.000 description 2
- PJVCZBRVTQZMAO-UHFFFAOYSA-N 6-chloro-5-[(3,5-dimethoxy-4-prop-1-en-2-ylphenyl)methyl]pyrimidine-2,4-diamine Chemical compound COC1=C(C(C)=C)C(OC)=CC(CC=2C(=NC(N)=NC=2N)Cl)=C1 PJVCZBRVTQZMAO-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 239000012876 carrier material Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- DNJIEGIFACGWOD-UHFFFAOYSA-N ethanethiol Chemical compound CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- CUONGYYJJVDODC-UHFFFAOYSA-N malononitrile Chemical compound N#CCC#N CUONGYYJJVDODC-UHFFFAOYSA-N 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 description 2
- 229940124530 sulfonamide Drugs 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- KJTLQQUUPVSXIM-ZCFIWIBFSA-N (R)-mevalonic acid Chemical compound OCC[C@](O)(C)CC(O)=O KJTLQQUUPVSXIM-ZCFIWIBFSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- RBNPOMFGQQGHHO-UHFFFAOYSA-N -2,3-Dihydroxypropanoic acid Natural products OCC(O)C(O)=O RBNPOMFGQQGHHO-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 1
- RDMMUSNZAWMFGX-UHFFFAOYSA-N 2,6-diamino-5-[(3,5-dimethoxy-4-prop-1-en-2-ylphenyl)methyl]-1h-pyrimidin-4-one Chemical compound COC1=C(C(C)=C)C(OC)=CC(CC=2C(=NC(N)=NC=2N)O)=C1 RDMMUSNZAWMFGX-UHFFFAOYSA-N 0.000 description 1
- CTPDSKVQLSDPLC-UHFFFAOYSA-N 2-(oxolan-2-ylmethoxy)ethanol Chemical compound OCCOCC1CCCO1 CTPDSKVQLSDPLC-UHFFFAOYSA-N 0.000 description 1
- WIISOYLZJJYTHT-UHFFFAOYSA-N 2-methyl-1h-pyrazol-5-one Chemical compound CN1C=CC(O)=N1 WIISOYLZJJYTHT-UHFFFAOYSA-N 0.000 description 1
- KPGXRSRHYNQIFN-UHFFFAOYSA-N 2-oxoglutaric acid Chemical compound OC(=O)CCC(=O)C(O)=O KPGXRSRHYNQIFN-UHFFFAOYSA-N 0.000 description 1
- BJNWKYCDRHYTSC-UHFFFAOYSA-N 3-amino-n-(4,5-dimethyl-1,2-oxazol-3-yl)benzenesulfonamide Chemical compound CC1=C(C)ON=C1NS(=O)(=O)C1=CC=CC(N)=C1 BJNWKYCDRHYTSC-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- UOQHWNPVNXSDDO-UHFFFAOYSA-N 3-bromoimidazo[1,2-a]pyridine-6-carbonitrile Chemical compound C1=CC(C#N)=CN2C(Br)=CN=C21 UOQHWNPVNXSDDO-UHFFFAOYSA-N 0.000 description 1
- SVDKVRZFBUISHD-UHFFFAOYSA-N 4-(2-hydroxypropan-2-yl)-3,5-dimethoxybenzaldehyde Chemical compound COC1=CC(C=O)=CC(OC)=C1C(C)(C)O SVDKVRZFBUISHD-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/48—Two nitrogen atoms
- C07D239/49—Two nitrogen atoms with an aralkyl radical, or substituted aralkyl radical, attached in position 5, e.g. trimethoprim
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/65—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by splitting-off hydrogen atoms or functional groups; by hydrogenolysis of functional groups
- C07C45/66—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by splitting-off hydrogen atoms or functional groups; by hydrogenolysis of functional groups by dehydration
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D295/145—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| LU77269A LU77269A1 (en, 2012) | 1977-05-05 | 1977-05-05 | |
| LU77.269 | 1977-05-05 | ||
| CH2650/78 | 1978-03-10 | ||
| CH265078A CH642637A5 (en) | 1977-05-05 | 1978-03-10 | Benzylpyrimidines and process for their preparation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1084498A true CA1084498A (en) | 1980-08-26 |
Family
ID=25691041
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA301,705A Expired CA1084498A (en) | 1977-05-05 | 1978-04-21 | Benzylpyrimidines and process for the preparation thereof |
Country Status (19)
| Country | Link |
|---|---|
| US (2) | US4203980A (en, 2012) |
| JP (1) | JPS53137978A (en, 2012) |
| AT (1) | ATA320578A (en, 2012) |
| BR (1) | BR7802834A (en, 2012) |
| CA (1) | CA1084498A (en, 2012) |
| DE (1) | DE2819212A1 (en, 2012) |
| DK (1) | DK143447C (en, 2012) |
| ES (1) | ES469450A1 (en, 2012) |
| FI (1) | FI781350A7 (en, 2012) |
| FR (1) | FR2389611B1 (en, 2012) |
| GB (1) | GB1583817A (en, 2012) |
| IL (1) | IL54598A0 (en, 2012) |
| IT (1) | IT1096292B (en, 2012) |
| MC (1) | MC1194A1 (en, 2012) |
| NL (1) | NL7804776A (en, 2012) |
| NO (1) | NO781587L (en, 2012) |
| NZ (1) | NZ187115A (en, 2012) |
| PT (1) | PT67994B (en, 2012) |
| SE (1) | SE7805186L (en, 2012) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4515948A (en) * | 1973-09-12 | 1985-05-07 | Hoffmann-La Roche Inc. | 2,4-Diamino-5-(4-amino and 4-dimethylamino-3,5-dimethoxy benzyl)pyrimidines |
| IT1138146B (it) * | 1981-08-11 | 1986-09-17 | Proter Spa | Processo per la produzione della 2,4-diammino-(3,5-dimetossi-4-metos sietossi-benzil)-pirimidina |
| JP5318757B2 (ja) * | 2006-06-16 | 2013-10-16 | ハー・ルンドベック・アクチエゼルスカベット | 神経因性疼痛の治療のための、組み合わされたセロトニンおよびノルエピネフリン再取り込み阻害を有する４−［２−（４−メチルフェニルスルファニル）−フェニル］ピペリジンの結晶形 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3996356A (en) * | 1969-07-02 | 1976-12-07 | Hoffmann-La Roche Inc. | Composition containing 5-sulfanilamido-3,4-dimethylisoxazole and a trimethoxybenzyl pyrimidine |
| BE795023A (fr) * | 1972-02-07 | 1973-08-06 | Hoffmann La Roche | Nouvelles benzylpyrimidines |
| US3985876A (en) * | 1973-01-05 | 1976-10-12 | Burroughs Wellcome Co. | Chemotherapeutic solutions containing a sulphur and a salt of a 2,4-diamino-5-benzylpyrimidine |
| US3931181A (en) * | 1973-07-27 | 1976-01-06 | Hoffmann-La Roche Inc. | 2,4-Diamino-5-benzylpyrimidines |
| CH598231A5 (en, 2012) | 1973-07-27 | 1978-04-28 | Hoffmann La Roche | |
| US4033962A (en) * | 1975-06-26 | 1977-07-05 | Hoffman-La Roche Inc. | 2,4-Diamino-pyrimidine derivatives and processes |
-
1978
- 1978-04-21 CA CA301,705A patent/CA1084498A/en not_active Expired
- 1978-04-26 US US05/900,357 patent/US4203980A/en not_active Expired - Lifetime
- 1978-04-28 NZ NZ187115A patent/NZ187115A/xx unknown
- 1978-04-30 IL IL54598A patent/IL54598A0/xx unknown
- 1978-05-02 FI FI781350A patent/FI781350A7/fi not_active Application Discontinuation
- 1978-05-02 MC MC781301A patent/MC1194A1/xx unknown
- 1978-05-02 DE DE19782819212 patent/DE2819212A1/de not_active Withdrawn
- 1978-05-03 NO NO781587A patent/NO781587L/no unknown
- 1978-05-03 AT AT320578A patent/ATA320578A/de not_active Application Discontinuation
- 1978-05-03 NL NL7804776A patent/NL7804776A/xx not_active Application Discontinuation
- 1978-05-03 DK DK195678A patent/DK143447C/da not_active IP Right Cessation
- 1978-05-03 FR FR7813130A patent/FR2389611B1/fr not_active Expired
- 1978-05-04 ES ES469450A patent/ES469450A1/es not_active Expired
- 1978-05-04 PT PT67994A patent/PT67994B/pt unknown
- 1978-05-04 GB GB17758/78A patent/GB1583817A/en not_active Expired
- 1978-05-04 JP JP5284378A patent/JPS53137978A/ja active Pending
- 1978-05-05 BR BR787802834A patent/BR7802834A/pt unknown
- 1978-05-05 IT IT23093/78A patent/IT1096292B/it active
- 1978-05-05 SE SE7805186A patent/SE7805186L/xx unknown
-
1979
- 1979-10-22 US US06/087,617 patent/US4254286A/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| FI781350A7 (fi) | 1978-11-06 |
| DE2819212A1 (de) | 1978-11-16 |
| FR2389611B1 (en, 2012) | 1980-06-20 |
| JPS53137978A (en) | 1978-12-01 |
| IL54598A0 (en) | 1978-07-31 |
| DK143447B (da) | 1981-08-24 |
| FR2389611A1 (en, 2012) | 1978-12-01 |
| PT67994A (en) | 1978-06-01 |
| NO781587L (no) | 1978-11-07 |
| PT67994B (en) | 1980-05-05 |
| GB1583817A (en) | 1981-02-04 |
| US4254286A (en) | 1981-03-03 |
| IT7823093A0 (it) | 1978-05-05 |
| IT1096292B (it) | 1985-08-26 |
| DK143447C (da) | 1982-01-04 |
| MC1194A1 (fr) | 1979-02-23 |
| ES469450A1 (es) | 1979-10-01 |
| NL7804776A (nl) | 1978-11-07 |
| ATA320578A (de) | 1980-03-15 |
| US4203980A (en) | 1980-05-20 |
| SE7805186L (sv) | 1978-11-06 |
| NZ187115A (en) | 1980-08-26 |
| DK195678A (da) | 1978-11-06 |
| BR7802834A (pt) | 1979-02-13 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |