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Sodium Bicarbonate → Benzyl 1-[({2,5-difluoro-4-[(2-{[(3-hydroxyazetidin-1-yl)carbonyl]amino}pyridin-4-yl)oxy]phenyl}amino)carbonyl]cyclopropanecarboxylate

HRID 388521
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HRID 388521 반응식
O([C:8]([NH:10][C:11]1[CH:16]=[C:15]([O:17][C:18]2[C:23]([F:24])=[CH:22][C:21]([NH:25][C:26]([C:28]3([C:31]([O:33][CH2:34][C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)=[O:32])[CH2:30][CH2:29]3)=[O:27])=[C:20]([F:41])[CH:19]=2)[CH:14]=[CH:13][N:12]=1)=[O:9])C1C=CC=CC=1.Cl.[OH:43][CH:44]1[CH2:47][NH:46][CH2:45]1.C(=O)([O-])O.[Na+]>CCCCCC.C(N(CC)CC)C.CN(C)C=O>[F:41][C:20]1[CH:19]=[C:18]([O:17][C:15]2[CH:14]=[CH:13][N:12]=[C:11]([NH:10][C:8]([N:46]3[CH2:47][CH:44]([OH:43])[CH2:45]3)=[O:9])[CH:16]=2)[C:23]([F:24])=[CH:22][C:21]=1[NH:25][C:26]([C:28]1([C:31]([O:33][CH2:34][C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=2)=[O:32])[CH2:29][CH2:30]1)=[O:27]
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참가 물질

7

반응물 3

HCID 516892Sodium BicarbonateHCID 27592903-Hydroxyazetidine hydrochloride2회HCID 24788625Benzyl 1-({[4-([2-[(phenoxycarbonyl)amino]pyridin-4-yl}oxy)-2,5-difluorophenyl]amino}carbonyl)cyclopropanecarboxylate

생성물 1

HCID 24788565Benzyl 1-[({2,5-difluoro-4-[(2-{[(3-hydroxyazetidin-1-yl)carbonyl]amino}pyridin-4-yl)oxy]phenyl}amino)carbonyl]cyclopropanecarboxylate수율 45.1%

시약·촉매·용매 3

HCID 6228Dimethylformamide용매HCID 8058Hexane용매HCID 8471Triethylamine용매2회

실험 절차

Triethylamine (0.100 ml) was added to a mixture of benzyl 1-({[4-({2-[(phenoxycarbonyl)amino]pyridin-4-yl}oxy)-2,5-difluorophenyl]amino}carbonyl)cyclopropanecarboxylate (200 mg), 3-hydroxyazetidine hydrochloride (39.1 mg) and N,N-dimethylformamide (4.0 ml) at room temperature under a nitrogen atmosphere, and the mixture was stirred for 6 hours and 10 minutes. 3-Hydroxyazetidine hydrochloride (10.0 mg) and triethylamine (0.025 ml) were added at room temperature, and the mixture was stirred for 1 hour and 20 minutes. A saturated aqueous solution of sodium hydrogencarbonate (16 ml) and hexane (5 ml) were added to the mixture, and the precipitated solid was collected by filtration. The solid was washed with water (2 ml, three times), and dried under aeration. The resultant solid was purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate, then ethyl acetate:methanol=10:1). The fractions containing the target compound was concentrated under reduced pressure to give the title compound (86.7 mg, 45%) as a white solid.

후처리

  1. stirringthe mixture was stirred for 1 hour and 20 minutes
  2. filtrationthe precipitated solid was collected by filtration
  3. washThe solid was washed with water (2 ml, three times)
  4. customdried under aeration
  5. customThe resultant solid was purified by silica gel column chromatography (Fuji Silysia NH, eluent
  6. additionThe fractions containing the target compound
  7. concentrationwas concentrated under reduced pressure

출처 및 근거

ORD 기록
ord-50a354f92f4245d384de59768fa51d85
출처 데이터셋
uspto-grants-2013_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08377938B2

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