1,2-Dichloroethane → methyl ((1S,2R,4R,6S)-2-((tert-butoxycarbonyl)amino)-4-(3-(6-(2,6-difluorophenyl)-5-fluoropicolinamido)pyridin-4-yl)-6-methylcyclohexyl)(methyl)carbamate

HRID 879220

반응식

HRID 879220 반응식
C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1.[NH2:15][C:16]1[CH:17]=[N:18][CH:19]=[CH:20][C:21]=1[C@@H:22]1[CH2:27][C@H:26]([CH3:28])[C@H:25]([N:29]([CH3:34])[C:30](=[O:33])[O:31][CH3:32])[C@H:24]([NH:35][C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:23]1.[F:43][C:44]1[CH:49]=[CH:48][CH:47]=[C:46]([F:50])[C:45]=1[C:51]1[N:56]=[C:55]([C:57]([OH:59])=[O:58])[CH:54]=[CH:53][C:52]=1[F:60]>CN(C=O)C.O>[C:39]([O:38][C:36]([NH:35][C@@H:24]1[CH2:23][C@H:22]([C:21]2[CH:20]=[CH:19][N:18]=[CH:17][C:16]=2[NH:15][C:57](=[O:58])[C:55]2[CH:54]=[CH:53][C:52]([F:60])=[C:51]([C:45]3[C:44]([F:43])=[CH:49][CH:48]=[CH:47][C:46]=3[F:50])[N:56]=2)[CH2:27][C@H:26]([CH3:28])[C@@H:25]1[N:29]([CH3:34])[C:30](=[O:33])[O:31][CH3:32])=[O:37])([CH3:41])([CH3:40])[CH3:42].[C:39]([O:38][C:36]([NH:35][C@H:24]1[CH2:23][C@@H:22]([C:21]2[CH:20]=[CH:19][N:18]=[CH:17][C:16]=2[NH:15][C:57](=[O:59])[C:55]2[CH:54]=[CH:53][C:52]([F:60])=[C:51]([C:45]3[C:46]([F:50])=[CH:47][CH:48]=[CH:49][C:44]=3[F:43])[N:56]=2)[CH2:27][C@@H:26]([CH3:28])[C@H:25]1[N:29]([CH3:34])[C:30](=[O:33])[O:31][CH3:32])=[O:37])([CH3:42])([CH3:41])[CH3:40]

참가 물질

8

반응물 4

HCID 111,2-DichloroethaneHCID 181649HOAtHCID 592265526-(2,6-Difluorophenyl)-5-fluoropicolinic acidHCID 86705269methyl ((1S,2R,4R,6S)-4-(3-aminopyridin-4-yl)-2-((tert-butoxycarbonyl)amino)-6-methylcyclohexyl)(methyl)carbamate

생성물 2

HCID 86705270methyl ((1S,2R,4R,6S)-2-((tert-butoxycarbonyl)amino)-4-(3-(6-(2,6-difluorophenyl)-5-fluoropicolinamido)pyridin-4-yl)-6-methylcyclohexyl)(methyl)carbamate수율 15%HCID 86705271methyl ((1R,2S,4S,6R)-2-((tert-butoxycarbonyl)amino)-4-(3-(6-(2,6-difluorophenyl)-5-fluoropicolinamido)pyridin-4-yl)-6-methylcyclohexyl)(methyl)carbamate수율 15%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

EDC (1.1 equiv.) and HOAt (1.1 equiv.) were added to a solution of (+/−)-methyl ((1S,2R,4R,6S)-4-(3-aminopyridin-4-yl)-2-((tert-butoxycarbonyl)amino)-6-methylcyclohexyl)(methyl)carbamate (1.0 equiv.) and 6-(2,6-difluorophenyl)-5-fluoropicolinic acid (1.5 equiv.) in DMF (0.05 M). The mixture was stirred at ambient temperature overnight. The reaction mixture was diluted with water and extracted with ethyl acetate. The combined extracts were washed sequentially with 1M aqueous sodium hydroxide and brine, dried over sodium sulfate, filtered, concentrated and purified by ISCO SiO2 chromatography. Purification was completed via SFC (40% EtOH, 100 mL/min, IC column) to yield methyl ((1S,2R,4R,6S)-2-((tert-butoxycarbonyl)amino)-4-(3-(6-(2,6-difluorophenyl)-5-fluoropicolinamido)pyridin-4-yl)-6-methylcyclohexyl)(methyl)carbamate (15% yield, 99% ee) and methyl ((1R,2S,4S,6R)-2-((tert-butoxycarbonyl)amino)-4-(3-(6-(2,6-difluorophenyl)-5-fluoropicolinamido)pyridin-4-yl)-6-methylcyclohexyl)(methyl)carbamate (15% yield, 99% ee). LC/MS (m/z)=628.3 (MH+), Rt=0.89 min.

후처리

  1. extractionextracted with ethyl acetate
  2. washThe combined extracts were washed sequentially with 1M aqueous sodium hydroxide and brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by ISCO SiO2 chromatography
  7. customPurification

출처 및 근거

ORD 기록
ord-d12edd5daef14496bbc8141cac919c3c
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08987457B2

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