1,8-Diazabicyclo(5.4.0)undec-7-ene → (4-(1-(3-(Cyanomethyl)-1-(ethylsulfonyl)azetidin-3-yl)-1H-pyrazol-4-yl)-7H-pyrrolo(2,3-d)pyrimidin-7-yl)methyl pivalate

HRID 1966187노트

반응식

HRID 1966187 반응식
[C:1]([O:7][CH2:8][N:9]1[C:13]2[N:14]=[CH:15][N:16]=[C:17]([C:18]3[CH:19]=[N:20][NH:21][CH:22]=3)[C:12]=2[CH:11]=[CH:10]1)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].[CH2:23]([S:25]([N:28]1[CH2:31][C:30](=[CH:32][C:33]#[N:34])[CH2:29]1)(=[O:27])=[O:26])[CH3:24].C1CCN2C(=NCCC2)CC1>CN(C)C=O.C1CCN2C(=NCCC2)CC1>[C:1]([O:7][CH2:8][N:9]1[C:13]2[N:14]=[CH:15][N:16]=[C:17]([C:18]3[CH:19]=[N:20][N:21]([C:30]4([CH2:32][C:33]#[N:34])[CH2:31][N:28]([S:25]([CH2:23][CH3:24])(=[O:27])=[O:26])[CH2:29]4)[CH:22]=3)[C:12]=2[CH:11]=[CH:10]1)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3]

참가 물질

6

반응물 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 578688542-(1-(Ethylsulfonyl)azetidin-3-ylidene)acetonitrileHCID 57868869(4-(1H-Pyrazol-4-yl)-7H-pyrrolo(2,3-d)pyrimidin-7-yl)methyl pivalate

생성물 1

HCID 66824167(4-(1-(3-(Cyanomethyl)-1-(ethylsulfonyl)azetidin-3-yl)-1H-pyrazol-4-yl)-7H-pyrrolo(2,3-d)pyrimidin-7-yl)methyl pivalate수율 89.5%

시약·촉매·용매 2

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-ene촉매HCID 6228Dimethylformamide용매

실험 절차

To a suspension of [4-(1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]methyl pivalate (19, 10.0 g, 33.4 mmol) and 2-(1-(ethylsulfonyl)azetidin-3-ylidene)acetonitrile (11, 6.22 g, 33.4 mmol, 1.0 equiv) in N,N-dimethylformamide (DMF, 20 mL) was added DBU (254 mg, 1.67 mmol, 0.05 equiv) drop wise to keep the reaction temperature between 15-25° C. After adding DBU, the reaction mixture became homogeneous within 90 min. The reaction mixture was stirred for 3 h at room temperature. When HPLC showed that the reaction was deemed complete, the reaction mixture was quenched with water (120 mL) and acetonitrile (80 mL). The resulting mixture was stirred at room temperature for an additional 30 min. The solids were collected by filtration, washed with a mixture of acetonitrile and water (⅔ by volume, 2×20 mL), and dried in vacuum oven at 40-45° C. for 24 h to afford crude (4-(1-(3-(cyanomethyl)-1-(ethylsulfonyl)azetidin-3-yl)-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl pivalate (20, 14.5 g, 16.2 g theoretical, 89.5% yield) as white solids, which was found to be sufficiently pure (>98.0% by HPLC) for the subsequent reaction without further purification. For 20:

후처리

  1. custombetween 15-25° C
  2. customthe reaction mixture was quenched with water (120 mL) and acetonitrile (80 mL)
  3. stirringThe resulting mixture was stirred at room temperature for an additional 30 min
  4. filtrationThe solids were collected by filtration
  5. washwashed with a mixture of acetonitrile and water (⅔ by volume, 2×20 mL)
  6. customdried in vacuum oven at 40-45° C. for 24 h

출처 및 근거

ORD 기록
ord-dc98a73a690847db95c0c12f08321cb4
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08420629B2

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