HRP20170851T1 - Postupak za proizvodnju cikloalkilkarboksiamido-piridin benzojevih kiselina - Google Patents
Postupak za proizvodnju cikloalkilkarboksiamido-piridin benzojevih kiselina Download PDFInfo
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- HRP20170851T1 HRP20170851T1 HRP20170851TT HRP20170851T HRP20170851T1 HR P20170851 T1 HRP20170851 T1 HR P20170851T1 HR P20170851T T HRP20170851T T HR P20170851TT HR P20170851 T HRP20170851 T HR P20170851T HR P20170851 T1 HRP20170851 T1 HR P20170851T1
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- 238000000034 method Methods 0.000 title claims 26
- 235000010233 benzoic acid Nutrition 0.000 title 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims 11
- 239000003960 organic solvent Substances 0.000 claims 11
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims 6
- 125000001931 aliphatic group Chemical group 0.000 claims 6
- 238000006243 chemical reaction Methods 0.000 claims 6
- TZKBVRDEOITLRB-UHFFFAOYSA-N 4-methyl-n-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[2-(1h-pyrazolo[3,4-b]pyridin-5-yl)ethynyl]benzamide Chemical compound C1CN(C)CCN1CC(C(=C1)C(F)(F)F)=CC=C1NC(=O)C1=CC=C(C)C(C#CC=2C=C3C=NNC3=NC=2)=C1 TZKBVRDEOITLRB-UHFFFAOYSA-N 0.000 claims 5
- 239000003795 chemical substances by application Substances 0.000 claims 5
- 150000004820 halides Chemical group 0.000 claims 5
- 230000002140 halogenating effect Effects 0.000 claims 5
- QCMHGCDOZLWPOT-FMNCTDSISA-N COC1=C(CC[C@@H]2CCC3=C(C2)C=CC(=C3)[C@H]2CC[C@](N)(CO)C2)C=CC=C1 Chemical compound COC1=C(CC[C@@H]2CCC3=C(C2)C=CC(=C3)[C@H]2CC[C@](N)(CO)C2)C=CC=C1 QCMHGCDOZLWPOT-FMNCTDSISA-N 0.000 claims 4
- 239000002253 acid Substances 0.000 claims 4
- 229910052736 halogen Inorganic materials 0.000 claims 4
- 150000002367 halogens Chemical class 0.000 claims 4
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims 4
- 229910052739 hydrogen Inorganic materials 0.000 claims 4
- 239000001257 hydrogen Substances 0.000 claims 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical group ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims 4
- VUDZSIYXZUYWSC-DBRKOABJSA-N (4r)-1-[(2r,4r,5r)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-hydroxy-1,3-diazinan-2-one Chemical compound FC1(F)[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)N[C@H](O)CC1 VUDZSIYXZUYWSC-DBRKOABJSA-N 0.000 claims 3
- MSSQOQPKGAMUSY-LEAFIULHSA-N 2-[1-[2-[(4r,6s)-8-chloro-6-(2,3-dimethoxyphenyl)-4,6-dihydropyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetyl]piperidin-4-yl]acetic acid Chemical compound COC1=CC=CC([C@@H]2C3=CC(Cl)=CC=C3N3C=CC=C3[C@@H](CC(=O)N3CCC(CC(O)=O)CC3)O2)=C1OC MSSQOQPKGAMUSY-LEAFIULHSA-N 0.000 claims 3
- WCDLCPLAAKUJNY-UHFFFAOYSA-N 4-[4-[3-(1h-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-6-yl]phenyl]morpholine Chemical compound C1COCCN1C1=CC=C(C2=CN3N=CC(=C3N=C2)C2=CNN=C2)C=C1 WCDLCPLAAKUJNY-UHFFFAOYSA-N 0.000 claims 3
- MITGKKFYIJJQGL-UHFFFAOYSA-N 9-(4-chlorobenzoyl)-6-methylsulfonyl-2,3-dihydro-1H-carbazol-4-one Chemical compound ClC1=CC=C(C(=O)N2C3=CC=C(C=C3C=3C(CCCC2=3)=O)S(=O)(=O)C)C=C1 MITGKKFYIJJQGL-UHFFFAOYSA-N 0.000 claims 3
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 claims 3
- HPKJGHVHQWJOOT-ZJOUEHCJSA-N N-[(2S)-3-cyclohexyl-1-oxo-1-({(2S)-1-oxo-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl}amino)propan-2-yl]-1H-indole-2-carboxamide Chemical compound C1C(CCCC1)C[C@H](NC(=O)C=1NC2=CC=CC=C2C=1)C(=O)N[C@@H](C[C@H]1C(=O)NCC1)C=O HPKJGHVHQWJOOT-ZJOUEHCJSA-N 0.000 claims 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical group [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims 3
- 239000003638 chemical reducing agent Substances 0.000 claims 3
- 229940125876 compound 15a Drugs 0.000 claims 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims 3
- FANCTJAFZSYTIS-IQUVVAJASA-N (1r,3s,5z)-5-[(2e)-2-[(1r,3as,7ar)-7a-methyl-1-[(2r)-4-(phenylsulfonimidoyl)butan-2-yl]-2,3,3a,5,6,7-hexahydro-1h-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol Chemical compound C([C@@H](C)[C@@H]1[C@]2(CCCC(/[C@@H]2CC1)=C\C=C\1C([C@@H](O)C[C@H](O)C/1)=C)C)CS(=N)(=O)C1=CC=CC=C1 FANCTJAFZSYTIS-IQUVVAJASA-N 0.000 claims 2
- VIMMECPCYZXUCI-MIMFYIINSA-N (4s,6r)-6-[(1e)-4,4-bis(4-fluorophenyl)-3-(1-methyltetrazol-5-yl)buta-1,3-dienyl]-4-hydroxyoxan-2-one Chemical compound CN1N=NN=C1C(\C=C\[C@@H]1OC(=O)C[C@@H](O)C1)=C(C=1C=CC(F)=CC=1)C1=CC=C(F)C=C1 VIMMECPCYZXUCI-MIMFYIINSA-N 0.000 claims 2
- IBYHHJPAARCAIE-UHFFFAOYSA-N 1-bromo-2-chloroethane Chemical compound ClCCBr IBYHHJPAARCAIE-UHFFFAOYSA-N 0.000 claims 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 2
- YLEIFZAVNWDOBM-ZTNXSLBXSA-N ac1l9hc7 Chemical compound C([C@H]12)C[C@@H](C([C@@H](O)CC3)(C)C)[C@@]43C[C@@]14CC[C@@]1(C)[C@@]2(C)C[C@@H]2O[C@]3(O)[C@H](O)C(C)(C)O[C@@H]3[C@@H](C)[C@H]12 YLEIFZAVNWDOBM-ZTNXSLBXSA-N 0.000 claims 2
- 125000003710 aryl alkyl group Chemical group 0.000 claims 2
- 125000003118 aryl group Chemical group 0.000 claims 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims 2
- 125000001072 heteroaryl group Chemical group 0.000 claims 2
- 239000003586 protic polar solvent Substances 0.000 claims 2
- SHAHPWSYJFYMRX-GDLCADMTSA-N (2S)-2-(4-{[(1R,2S)-2-hydroxycyclopentyl]methyl}phenyl)propanoic acid Chemical compound C1=CC([C@@H](C(O)=O)C)=CC=C1C[C@@H]1[C@@H](O)CCC1 SHAHPWSYJFYMRX-GDLCADMTSA-N 0.000 claims 1
- TWYYFYNJOJGNFP-CUXYNZQBSA-N (2s,4r,5s,6s)-2-[(4s,5r)-4-acetyloxy-5-methyl-3-methylidene-6-phenylhexyl]-2-carbamoyl-4-[[(e,4s,6s)-4,6-dimethyloct-2-enoyl]oxymethyl]-5-hydroxy-1,3-dioxane-4,5,6-tricarboxylic acid Chemical compound O1[C@H](C(O)=O)[C@](C(O)=O)(O)[C@](COC(=O)/C=C/[C@@H](C)C[C@@H](C)CC)(C(O)=O)O[C@]1(C(N)=O)CCC(=C)[C@@H](OC(C)=O)[C@H](C)CC1=CC=CC=C1 TWYYFYNJOJGNFP-CUXYNZQBSA-N 0.000 claims 1
- IGVKWAAPMVVTFX-BUHFOSPRSA-N (e)-octadec-5-en-7,9-diynoic acid Chemical compound CCCCCCCCC#CC#C\C=C\CCCC(O)=O IGVKWAAPMVVTFX-BUHFOSPRSA-N 0.000 claims 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims 1
- JEDZLBFUGJTJGQ-UHFFFAOYSA-N [Na].COCCO[AlH]OCCOC Chemical group [Na].COCCO[AlH]OCCOC JEDZLBFUGJTJGQ-UHFFFAOYSA-N 0.000 claims 1
- 238000005576 amination reaction Methods 0.000 claims 1
- 125000003277 amino group Chemical group 0.000 claims 1
- 239000000010 aprotic solvent Substances 0.000 claims 1
- 239000003054 catalyst Substances 0.000 claims 1
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical group N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 claims 1
- 238000006880 cross-coupling reaction Methods 0.000 claims 1
- 238000005658 halogenation reaction Methods 0.000 claims 1
- 150000004678 hydrides Chemical group 0.000 claims 1
- 150000007529 inorganic bases Chemical class 0.000 claims 1
- 150000007522 mineralic acids Chemical class 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 230000001590 oxidative effect Effects 0.000 claims 1
- 125000004076 pyridyl group Chemical group 0.000 claims 1
- 238000006722 reduction reaction Methods 0.000 claims 1
- 239000011435 rock Substances 0.000 claims 1
- 239000012419 sodium bis(2-methoxyethoxy)aluminum hydride Substances 0.000 claims 1
- -1 sulfonyl compound Chemical class 0.000 claims 1
- 229910052723 transition metal Inorganic materials 0.000 claims 1
- 150000003624 transition metals Chemical class 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/73—Unsubstituted amino or imino radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/433—Thidiazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/08—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing alicyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Claims (25)
1. Postupak za pripremu spoja formule 1:
[image]
obuhvaćajući korak:
ia) reagiranja spoja formule 6a:
[image]
pri čemu,
R je H, C1-6 alifatični, aril, aralkil, heteroaril, cikloalkil, ili heterocikloalkil;
R1 je nezavisno izabran od -RJ, -ORJ, -N(RJ)2, -NO2, halogena, -CN, -C1-4haloalkila, -C1-4haloalkoksi,
-C(O)N(RJ)2, -NRJC(O)RJ, -SORJ, -SO2RJ, -SO2N(RJ)2, -NRJSO2RJ, -CORJ, -CO2RJ, -NRJSO2N(RJ)2,-COCORJ;
RJ je vodik ili C1-6 alifatični;
O je cijeli broj od 0 do zaključno 3; i
p je cijeli broj od 0 do zaključno 5;
sa spojem formule 7a:
[image]
pri čemu,
A je fuzionirani heterocikloalkilni prsten;
R1 je nezavisno izabran od -RJ, -ORJ, -N(RJ)2, -NO2, halogena, -CN, -C1-4haloalkila, -C1-4 haloalkoksi,
-C(O)N(RJ)2, -NRJC(O)RJ, -SORJ, -SO2RJ, -SO2N(RJ)2,-NRJSO2RJ, -CORJ, -CO2RJ, -NRJSO2N(RJ)2, -COCORJ;
RJ je vodik ili C1-6 alifatični;
m je cijeli broj od 0 do zaključno 3;
n je cijeli broj od 1 do zaključno 4; i
X je halid ili OH;
u organskom otapalu u prisustvu baze;
pri čemu je spoj formule 6a pripremljen prema sljedećim koracima:
ib) osiguravanje spoja 2a i spoja 3a,
[image]
pri čemu,
R1 je nezavisno izabran od -RJ, -ORJ, -N(RJ)2, -NO2, halogena, -CN, -C1-4haloalkila, -C1-4haloalkoksi,
-C(O)N(RJ)2, -NRJC(O)RJ, -SORJ, -SO2RJ, -SO2N(RJ)2, -NRJSO2RJ, -CORJ, -CO2RJ, -NRJSO2N(RJ)2,
-COCORJ ;
RJ je vodik ili C1-6 alifatični;
o je cijeli broj od 0 do zaključno 4; i
p je cijeli broj od 0 do zaključno 5;
iib) unakrsno spajanje spoja 2a i spoja 3a u dvofaznoj smjesi sadržavajući vodu, organsko otapalo, bazu, i katalizator prijelaznog metala da se dobije spoje 4a,
[image]
pri čemu, R1, o, i p su kao što je definirano za spojeve 2a i 3a iznad;
iiib) oksidirajući spoj 4a da se dobije spoj 5a,
[image]
pri čemu, R1, o, i p su kao što je gore definirano za spoja 2a i 3a;
ivb) dodajući amino grupu na poziciju 6 piridil ostatka da se dobije spoj 6a,
[image]
pri čemu se reakcija aminacije izvodi u prisustvu sulfonil spoja, i pri čemu R je H, C1-6alifatični, aril, aralkil, heteroaril, cikloalkil, ili heterocikloalkil i R1, o, i p su kao što je gore definirano za spojeve 2a i 3a.
2. Postupak prema patentnom zahtjevu 1, pri čemu je spoj 7a pripremljen prema sljedećim koracima:
ic) reducirajući Spoj 10a u organskom otapalu:
[image]
pri čemu,
A je fuzionirani heterocikloalkil;
R1 je nezavisno izabran od -RJ, -ORJ, -N(RJ)2, -NO2, halogena, -CN, -C1-4haloalkila, -C1-4haloalkoksi,
-C(O)N(RJ)2, -NRJC(O)RJ, -SORJ, -SO2RJ, -SO2N(RJ)2,-NRJSO2RJ, -CORJ, -CO2RJ, -NRJSO2N(RJ)2, -COCORJ;
RJ je vodik ili C1-6 alifatični; i
m je cijeli broj od 0 do zaključno 3,
sa reducirajućim agensom da se dobije Spoj 11a:
[image]
pri čemu, prsten A, R1, i m su kao što je definirano u Spoju 10a iznad;
iic) reagiranjem Spoja 11a sa prvim halogenirajućim agensom u organskom rastvaraču da se dobije Spoj 12a:
[image]
pri čemu, prsten A, R1, i m su kao što je definirano u Spoju 10a iznad, i Hal je halid;
iiic) reagiranjem Spoja 12a sa cijanidom da se dobije Spoj 13a:
[image]
pri čemu, prsten A, R1, i m su kao što je definirano u Spoju 10a iznad;
ivc) reagiranjem Spoja 13a sa spojem formule 13aa u prisustvu baze:
[image]
pri čemu,
Hal je halid; i
q je cijeli broj od 0 do zaključno 3; da se dobije spoje formule 14a:
[image]
pri čemu,
r je cijeli broj od 1 do zaključno 4; i
prsten A, R1, i m su kao što je definirano u Spoju 10a iznad;
vc) sekvencijalnim reagiranjem Spoja 14a sa hidroksidnom bazom i kiselinom da se formira Spoj 15a, koji je spoj 7a, kada je X = OH:
[image]
pri čemu, r, prsten A, R1, i m su kao što je definirano u Spoju 14a iznad; i
vic) reagiranjem Spoja 15a sa drugim agensom za halogeniranje u organskom otapalu da se formira Spoj 16a, koji je spoj 7a kada je X = halid:
[image]
pri čemu,
Hal je halid; i
r, prsten A, R1, i m su kao što je definirano u Spoju 14a iznad.
3. Postupak prema patentnom zahtjevu 2, pri čemu je organsko otapalo korišteno u koraku ic, neprotonsko otapalo.
4. Postupak prema patentnom zahtjevu 2, pri čemu je organsko otapalo korišteno u koraku ic, toluen.
5. Postupak prema patentnom zahtjevu 2, pri čemu je reducirajući agens hidrid.
6. Postupak prema patentnom zahtjevu 2, pri čemu je reducirajući agens natrij bis(2-metoksietoksi)aluminij hidrid.
7. Postupak prema patentnom zahtjevu 2, pri čemu se reakcija redukcije odvija između 15°C i 40°C.
8. Postupak prema patentnom zahtjevu 2, pri čemu je organsko otapalo korišteno u koraku iic, neprotonsko otapalo.
9. Postupak prema patentnom zahtjevu 2, pri čemu je organsko otapalo korišteno u koraku iic, metil t-butil eter.
10. Postupak prema patentnom zahtjevu 2, pri čemu je prvi halogenirajući agens tionil klorid.
11. Postupak prema patentnom zahtjevu 2, pri čemu se reakcija Spoja 11a sa prvom reakcijom halogeniziranja odvija između 15°C i 30°C.
12. Postupak prema patentnom zahtjevu 2, pri čemu je cijanid, natrij cijanid.
13. Postupak prema patentnom zahtjevu 2, pri čemu se reakcija Spoja 12a sa cijanidom odvija između 30°C i 40°C.
14. Postupak prema patentnom zahtjevu 2, pri čemu je baza u koraku ivc, neorganska baza.
15. Postupak prema patentnom zahtjevu 2, pri čemu je baza u koraku ivc, kalij hidroksid.
16. Postupak prema patentnom zahtjevu 2, pri čemu je Spoj 13aa, 1-bromo-2-kloroetan.
17. Postupak prema patentnom zahtjevu 2, pri čemu se reakcija Spoja 13a sa spojem formule 13aa odvija između 50°C i 90°C.
18. Postupak prema patentnom zahtjevu 2, pri čemu je hidroksidna baza natrij hidroksid.
19. Postupak prema patentnom zahtjevu 2, pri čemu je kiselina u koraku vc, neorganska kiselina.
20. Postupak prema patentnom zahtjevu 2, pri čemu je kiselina u koraku vc, klorovodična kiselina.
21. Postupak prema patentnom zahtjevu 2, pri čemu se sekvencijalna reakcija Spoja 14a sa hidroksidnom bazom i kiselinom odvija između 70°C i 90°C.
22. Postupak prema patentnom zahtjevu 2, pri čemu je organsko otapalo u koraku vic, neprotonsko otapalo.
23. Postupak prema patentnom zahtjevu 2, pri čemu je organski rastvarač u koraku vic, toluen.
24. Postupak prema patentnom zahtjevu 2, pri čemu je drugi halogenirajući agens tionil klorid.
25. Postupak prema patentnom zahtjevu 2, pri čemu se reakcija Spoja 15a sa drugim halogenirajućim agensom odvija između 40°C i 80°C.
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