JPH0565517B2

JPH0565517B2 -

Info

Publication number: JPH0565517B2
Authority: JP; Japan
Prior art keywords: group; compound; groups; derivative; chloroform
Prior art date: 1982-01-15
Legal status : Expired - Lifetime

Application number

JP835178A

Other languages

English (en)

Japanese (ja)

Other versions

JPS58170797A (ja

Inventor

Puchito Moorisu

Jakine Jannkuroodo

Shinee Pieeru

Shoai Jan

Rorumo Jannkuroodo

Naasuru Maamuudo

Current Assignee

ERU O PE I SE SOC SHIBIRU

Original Assignee

ERU O PE I SE SOC SHIBIRU

Priority date

1982-01-15

Filing date

1983-01-14

Publication date

1993-09-17

1983-01-14 Application filed by ERU O PE I SE SOC SHIBIRU filed Critical ERU O PE I SE SOC SHIBIRU

1983-10-07 Publication of JPS58170797A publication Critical patent/JPS58170797A/ja

1993-09-17 Publication of JPH0565517B2 publication Critical patent/JPH0565517B2/ja

Status Granted legal-status Critical Current

Links

150000001875 compounds Chemical class 0.000 claims description 144
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 142
150000002016 disaccharides Chemical class 0.000 claims description 102
230000015572 biosynthetic process Effects 0.000 claims description 100
238000003786 synthesis reaction Methods 0.000 claims description 93
238000006243 chemical reaction Methods 0.000 claims description 85
229920001542 oligosaccharide Polymers 0.000 claims description 82
150000002482 oligosaccharides Chemical class 0.000 claims description 81
238000000034 method Methods 0.000 claims description 75
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 60
239000002904 solvent Substances 0.000 claims description 54
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 51
125000006239 protecting group Chemical group 0.000 claims description 35
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 32
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 31
125000001424 substituent group Chemical group 0.000 claims description 30
239000002253 acid Substances 0.000 claims description 27
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 27
238000005670 sulfation reaction Methods 0.000 claims description 26
230000008569 process Effects 0.000 claims description 24
230000019635 sulfation Effects 0.000 claims description 23
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 21
239000003054 catalyst Substances 0.000 claims description 20
125000000524 functional group Chemical group 0.000 claims description 19
150000002905 orthoesters Chemical class 0.000 claims description 18
239000002243 precursor Substances 0.000 claims description 18
150000003839 salts Chemical class 0.000 claims description 17
QAOWNCQODCNURD-UHFFFAOYSA-L sulfate group Chemical group S(=O)(=O)([O-])[O-] QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 16
238000006206 glycosylation reaction Methods 0.000 claims description 15
AEMOLEFTQBMNLQ-CLQWQSTFSA-N l-iduronic acid Chemical compound O[C@H]1O[C@H](C(O)=O)[C@H](O)[C@@H](O)[C@@H]1O AEMOLEFTQBMNLQ-CLQWQSTFSA-N 0.000 claims description 15
125000000217 alkyl group Chemical group 0.000 claims description 14
125000002252 acyl group Chemical group 0.000 claims description 13
MSWZFWKMSRAUBD-QZABAPFNSA-N beta-D-glucosamine Chemical compound N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-QZABAPFNSA-N 0.000 claims description 13
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 13
HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 claims description 12
229960002897 heparin Drugs 0.000 claims description 12
239000002808 molecular sieve Substances 0.000 claims description 12
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 claims description 12
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 11
229910052799 carbon Inorganic materials 0.000 claims description 11
150000004820 halides Chemical class 0.000 claims description 11
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 10
IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 claims description 10
AEMOLEFTQBMNLQ-WAXACMCWSA-N alpha-D-glucuronic acid Chemical compound O[C@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-WAXACMCWSA-N 0.000 claims description 10
150000001412 amines Chemical class 0.000 claims description 10
MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 claims description 10
238000009833 condensation Methods 0.000 claims description 10
230000005494 condensation Effects 0.000 claims description 10
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
229920002971 Heparan sulfate Polymers 0.000 claims description 8
125000003277 amino group Chemical group 0.000 claims description 8
239000003795 chemical substances by application Substances 0.000 claims description 8
238000007306 functionalization reaction Methods 0.000 claims description 8
230000013595 glycosylation Effects 0.000 claims description 8
239000007858 starting material Substances 0.000 claims description 8
238000006482 condensation reaction Methods 0.000 claims description 7
239000012298 atmosphere Substances 0.000 claims description 6
230000007062 hydrolysis Effects 0.000 claims description 6
238000006460 hydrolysis reaction Methods 0.000 claims description 6
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
125000000547 substituted alkyl group Chemical group 0.000 claims description 6
230000001180 sulfating effect Effects 0.000 claims description 6
125000003158 alcohol group Chemical group 0.000 claims description 5
238000009835 boiling Methods 0.000 claims description 5
239000003960 organic solvent Substances 0.000 claims description 5
238000007127 saponification reaction Methods 0.000 claims description 5
230000009471 action Effects 0.000 claims description 4
WQZGKKKJIJFFOK-ZNVMLXAYSA-N L-idopyranose Chemical compound OC[C@@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-ZNVMLXAYSA-N 0.000 claims description 3
150000003467 sulfuric acid derivatives Chemical class 0.000 claims description 3
238000009903 catalytic hydrogenation reaction Methods 0.000 claims description 2
150000002463 imidates Chemical class 0.000 claims description 2
239000011261 inert gas Substances 0.000 claims description 2
150000002730 mercury Chemical class 0.000 claims description 2
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 claims 2
239000002168 alkylating agent Substances 0.000 claims 2
229940100198 alkylating agent Drugs 0.000 claims 2
125000003700 epoxy group Chemical group 0.000 claims 2
125000004036 acetal group Chemical group 0.000 claims 1
239000012345 acetylating agent Substances 0.000 claims 1
230000029936 alkylation Effects 0.000 claims 1
238000005804 alkylation reaction Methods 0.000 claims 1
CEIPQQODRKXDSB-UHFFFAOYSA-N ethyl 3-(6-hydroxynaphthalen-2-yl)-1H-indazole-5-carboximidate dihydrochloride Chemical compound Cl.Cl.C1=C(O)C=CC2=CC(C3=NNC4=CC=C(C=C43)C(=N)OCC)=CC=C21 CEIPQQODRKXDSB-UHFFFAOYSA-N 0.000 claims 1
230000014759 maintenance of location Effects 0.000 claims 1
239000002516 radical scavenger Substances 0.000 claims 1
238000007142 ring opening reaction Methods 0.000 claims 1
238000009938 salting Methods 0.000 claims 1
230000002194 synthesizing effect Effects 0.000 claims 1
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 342
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 204
239000000243 solution Substances 0.000 description 188
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 182
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 170
239000000203 mixture Substances 0.000 description 156
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 117
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 85
239000000047 product Substances 0.000 description 77
239000011541 reaction mixture Substances 0.000 description 77
239000000741 silica gel Substances 0.000 description 71
229910002027 silica gel Inorganic materials 0.000 description 71
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 61
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 61
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 54
238000003756 stirring Methods 0.000 description 52
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 49
238000004519 manufacturing process Methods 0.000 description 49
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 40
238000001704 evaporation Methods 0.000 description 40
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 39
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 39
229910052938 sodium sulfate Inorganic materials 0.000 description 38
235000011152 sodium sulphate Nutrition 0.000 description 38
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 37
238000000921 elemental analysis Methods 0.000 description 36
239000006188 syrup Substances 0.000 description 36
235000020357 syrup Nutrition 0.000 description 36
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 35
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 34
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
230000008020 evaporation Effects 0.000 description 32
239000012071 phase Substances 0.000 description 31
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 27
-1 acids Aminosugars Chemical class 0.000 description 26
239000012074 organic phase Substances 0.000 description 26
150000002772 monosaccharides Chemical class 0.000 description 25
150000004044 tetrasaccharides Chemical class 0.000 description 25
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 24
238000001816 cooling Methods 0.000 description 22
238000002360 preparation method Methods 0.000 description 22
239000007787 solid Substances 0.000 description 22
239000000126 substance Substances 0.000 description 22
238000004587 chromatography analysis Methods 0.000 description 21
150000004043 trisaccharides Chemical class 0.000 description 21
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 20
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 20
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 19
239000007788 liquid Substances 0.000 description 19
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 19
238000004458 analytical method Methods 0.000 description 18
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 17
238000001035 drying Methods 0.000 description 17
238000001914 filtration Methods 0.000 description 17
238000005481 NMR spectroscopy Methods 0.000 description 16
230000007935 neutral effect Effects 0.000 description 16
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 15
235000008504 concentrate Nutrition 0.000 description 15
239000012141 concentrate Substances 0.000 description 15
239000000543 intermediate Substances 0.000 description 15
239000000843 powder Substances 0.000 description 15
238000010828 elution Methods 0.000 description 14
239000005457 ice water Substances 0.000 description 14
KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
239000011734 sodium Substances 0.000 description 14
235000017557 sodium bicarbonate Nutrition 0.000 description 14
229910000030 sodium bicarbonate Inorganic materials 0.000 description 14
235000000346 sugar Nutrition 0.000 description 14
238000012546 transfer Methods 0.000 description 14
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 13
239000003153 chemical reaction reagent Substances 0.000 description 13
239000000284 extract Substances 0.000 description 13
229910052739 hydrogen Inorganic materials 0.000 description 13
239000011347 resin Substances 0.000 description 13
229920005989 resin Polymers 0.000 description 13
YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 12
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
239000012300 argon atmosphere Substances 0.000 description 11
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Substances ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 11
229930014626 natural product Natural products 0.000 description 11
229910052757 nitrogen Inorganic materials 0.000 description 11
AKEJUJNQAAGONA-UHFFFAOYSA-N sulfur trioxide Inorganic materials O=S(=O)=O AKEJUJNQAAGONA-UHFFFAOYSA-N 0.000 description 11
GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 11
BWZVCCNYKMEVEX-UHFFFAOYSA-N 2,4,6-Trimethylpyridine Chemical compound CC1=CC(C)=NC(C)=C1 BWZVCCNYKMEVEX-UHFFFAOYSA-N 0.000 description 10
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
239000007864 aqueous solution Substances 0.000 description 10
238000007865 diluting Methods 0.000 description 10
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 10
239000001257 hydrogen Substances 0.000 description 10
UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 10
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 10
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 9
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
229920000669 heparin Polymers 0.000 description 9
238000005984 hydrogenation reaction Methods 0.000 description 9
238000002329 infrared spectrum Methods 0.000 description 9
239000008194 pharmaceutical composition Substances 0.000 description 9
229920001467 poly(styrenesulfonates) Polymers 0.000 description 9
229910052708 sodium Inorganic materials 0.000 description 9
238000001228 spectrum Methods 0.000 description 9
150000008163 sugars Chemical class 0.000 description 9
238000005406 washing Methods 0.000 description 9
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 8
208000007536 Thrombosis Diseases 0.000 description 8
150000001768 cations Chemical class 0.000 description 8
239000003480 eluent Substances 0.000 description 8
230000011987 methylation Effects 0.000 description 8
238000007069 methylation reaction Methods 0.000 description 8
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 8
WQZGKKKJIJFFOK-SVZMEOIVSA-N (+)-Galactose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-SVZMEOIVSA-N 0.000 description 7
UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical class O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 7
229920002683 Glycosaminoglycan Polymers 0.000 description 7
230000002378 acidificating effect Effects 0.000 description 7
238000005893 bromination reaction Methods 0.000 description 7
230000000694 effects Effects 0.000 description 7
ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 7
239000012634 fragment Substances 0.000 description 7
229930182470 glycoside Natural products 0.000 description 7
230000003287 optical effect Effects 0.000 description 7
238000000746 purification Methods 0.000 description 7
239000012429 reaction media Substances 0.000 description 7
238000012360 testing method Methods 0.000 description 7
JQSHBVHOMNKWFT-DTORHVGOSA-N varenicline Chemical compound C12=CC3=NC=CN=C3C=C2[C@H]2C[C@@H]1CNC2 JQSHBVHOMNKWFT-DTORHVGOSA-N 0.000 description 7
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 6
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 6
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 6
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
229910052770 Uranium Inorganic materials 0.000 description 6
238000006640 acetylation reaction Methods 0.000 description 6
PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 6
229960002246 beta-d-glucopyranose Drugs 0.000 description 6
WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 6
150000002148 esters Chemical class 0.000 description 6
230000006870 function Effects 0.000 description 6
239000011521 glass Substances 0.000 description 6
150000002338 glycosides Chemical class 0.000 description 6
239000002609 medium Substances 0.000 description 6
NGYIMTKLQULBOO-UHFFFAOYSA-L mercury dibromide Chemical compound Br[Hg]Br NGYIMTKLQULBOO-UHFFFAOYSA-L 0.000 description 6
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 6
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
229920006395 saturated elastomer Polymers 0.000 description 6
239000000377 silicon dioxide Substances 0.000 description 6
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
239000000725 suspension Substances 0.000 description 6
LJIOTBMDLVHTBO-CUYJMHBOSA-N (2s)-2-amino-n-[(1r,2r)-1-cyano-2-[4-[4-(4-methylpiperazin-1-yl)sulfonylphenyl]phenyl]cyclopropyl]butanamide Chemical compound CC[C@H](N)C(=O)N[C@]1(C#N)C[C@@H]1C1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)N2CCN(C)CC2)C=C1 LJIOTBMDLVHTBO-CUYJMHBOSA-N 0.000 description 5
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