Pyridine → 1,1-dimethylethyl 3-[({3-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}-5-[(3-methyl-4-oxo-3,4-dihydro-2H-1,3-benzoxazin-7-yl)oxy]phenyl}carbonyl)amino]-1H-pyrazole-1-carboxylate

HRID 548732노트

반응식

HRID 548732 반응식
ClC(N(C)C)=C(C)C.[CH3:9][C@H:10]([O:14][C:15]1[CH:16]=[C:17]([CH:21]=[C:22]([O:24][C:25]2[CH:36]=[CH:35][C:28]3[C:29](=[O:34])[N:30]([CH3:33])[CH2:31][O:32][C:27]=3[CH:26]=2)[CH:23]=1)[C:18]([OH:20])=O)[CH2:11][O:12][CH3:13].[NH2:37][C:38]1[CH:42]=[CH:41][N:40]([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[N:39]=1.N1C=CC=CC=1>C(Cl)Cl>[CH3:9][C@H:10]([O:14][C:15]1[CH:16]=[C:17]([C:18]([NH:37][C:38]2[CH:42]=[CH:41][N:40]([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[N:39]=2)=[O:20])[CH:21]=[C:22]([O:24][C:25]2[CH:36]=[CH:35][C:28]3[C:29](=[O:34])[N:30]([CH3:33])[CH2:31][O:32][C:27]=3[CH:26]=2)[CH:23]=1)[CH2:11][O:12][CH3:13]

참가 물질

6

반응물 4

HCID 1049PyridineHCID 6407921-Chloro-N,N-2-trimethylpropenylamineHCID 51358380tert-Butyl 3-amino-1H-pyrazole-1-carboxylateHCID 576631913-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}-5-[(3-methyl-4-oxo-3,4-dihydro-2H-1,3-benzoxazin-7-yl)oxy]benzoic acid

생성물 1

HCID 576632111,1-dimethylethyl 3-[({3-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}-5-[(3-methyl-4-oxo-3,4-dihydro-2H-1,3-benzoxazin-7-yl)oxy]phenyl}carbonyl)amino]-1H-pyrazole-1-carboxylate수율 52.9%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

1-Chloro-N,N,2-trimethyl-1-propenylamine (0.13 mL, 0.97 mmol) was added to a solution of 3-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}-5-[(3-methyl-4-oxo-3,4-dihydro-2H-1,3-benzoxazin-7-yl)oxy]benzoic acid (0.25 g, 0.65 mmol) in DCM (10 mL) and stirred for 1 hour. 1,1-Dimethylethyl 3-amino-1H-pyrazole-1-carboxylate (0.18 g, 0.97 mmol) then pyridine (0.11 mL, 1.29 mmol) were added and the reaction stirred for a further 45 mins then reduced in vacuo and partitioned between ethyl acetate (50 mL) and water (50 mL). The aqueous layer was further extracted into ethyl acetate (50 mL) and the combined organics washed with water (50 mL), brine (50 mL), dried (MgSO4), and reduced in vacuo. The crude oil was chromatographed on silica, eluting with 40-100% ethyl acetate in isohexane, to give the desired compound as a golden oil (0.19 g). 1H NMR δ (CDCl3): 1.32 (d, 3H), 1.63 (s, 9H), 3.10 (s, 3H), 3.40 (s, 3H), 3.48-3.60 (m, 2H), 4.56-4.60 (m, 1H), 5.18 (s, 2H), 6.54 (d, 1H), 6.73-6.76 (m, 1H), 6.83 (t, 1H), 7.07-7.08 (m, 2H), 7.25-7.26 (m, 1H), 7.95 (d, 1H), 8.00 (d, 1H), 8.65 (s, 1H); m/z 551 (M−H)−

후처리

  1. stirringthe reaction stirred for a further 45 mins
  2. custompartitioned between ethyl acetate (50 mL) and water (50 mL)
  3. extractionThe aqueous layer was further extracted into ethyl acetate (50 mL)
  4. washthe combined organics washed with water (50 mL), brine (50 mL)
  5. dry with materialdried (MgSO4)
  6. customThe crude oil was chromatographed on silica
  7. washeluting with 40-100% ethyl acetate in isohexane

출처 및 근거

ORD 기록
ord-527929032d744d3e81f1d228b9b5d771
출처 데이터셋
uspto-grants-2011_05
특허 번호
US07943607B2

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