5-Ethoxypyridin-2-amine → {1-[4-(6-Ethoxy-3-phenyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester

HRID 872303노트

반응식

HRID 872303 반응식
[C:1]([O:5][C:6](=[O:28])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18](=O)[CH:19](Br)[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[NH2:29][C:30]1[CH:35]=[CH:34][C:33]([O:36][CH2:37][CH3:38])=[CH:32][N:31]=1>C(O)C>[C:1]([O:5][C:6](=[O:28])[NH:7][C:8]1([C:12]2[CH:13]=[CH:14][C:15]([C:18]3[N:29]=[C:30]4[CH:35]=[CH:34][C:33]([O:36][CH2:37][CH3:38])=[CH:32][N:31]4[C:19]=3[C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)=[CH:16][CH:17]=2)[CH2:9][CH2:10][CH2:11]1)([CH3:3])([CH3:2])[CH3:4]

참가 물질

4

반응물 2

HCID 193671035-Ethoxypyridin-2-amineHCID 86691038tert-Butyl (1-{4-[bromo(phenyl)acetyl]phenyl}cyclobutyl)carbamate

생성물 1

HCID 66665892{1-[4-(6-Ethoxy-3-phenyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester수율 28%

시약·촉매·용매 1

HCID 702Ethanol용매

실험 절차

A mixture of {1-[4-(2-bromo-2-phenyl-acetyl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester [Int-1-A] (0.87 g, 2.0 mmol), 2-amino-5-ethoxypyridine (0.54 g, 3.9 mmol, 2 equiv) and powdered activated 3A sieves (10 g) in ethanol (7.3 mL) was heated for 5 h at the reflux temperature with monitoring by UPLC-MS. The resulting solution was separated between CH2Cl2 (25 mL) and an saturated aqueous NaHCO3 solution (25 mL). The organic phase was washed with a saturated aqueous NaCl solution (25 mL), dried (Na2SO4 anh), and concentrated under reduced pressure. The remaining material was purified using MPLC (Biotage Isolera; 25 g SNAP cartridge: 100% hexane for 1.5 min., gradient to 80% hexane/20% EtOAc over 2.2 min., gradient to 70% hexane/30% EtOAc over 10.6 min., 70% hexane/30% EtOAc for 2.8 min., gradient to 65% hexane/35% EtOAc over 2.2 min., 65% hexane/35% EtOAc for 4.8 min.) to give {1-[4-(6-ethoxy-3-phenyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester (0.26 g, 28%):

후처리

  1. temperaturewas heated for 5 h at the reflux temperature with monitoring by UPLC-MS
  2. customThe resulting solution was separated between CH2Cl2 (25 mL)
  3. washThe organic phase was washed with a saturated aqueous NaCl solution (25 mL)
  4. dry with materialdried (Na2SO4 anh)
  5. concentrationconcentrated under reduced pressure
  6. customThe remaining material was purified
  7. customMPLC (Biotage Isolera; 25 g SNAP cartridge: 100% hexane for 1.5 min., gradient to 80% hexane/20% EtOAc over 2.2 min., gradient to 70% hexane/30% EtOAc over 10.6 min., 70% hexane/30% EtOAc for 2.8 min., gradient to 65% hexane/35% EtOAc over 2.2 min., 65% hexane/35% EtOAc for 4.8 min.)

출처 및 근거

ORD 기록
ord-ff9162036e6c470397343a3c54860156
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08975265B2

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