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Acryloyl chloride → N-{5-[(5-Chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)amino]-2-[(3R)-3-dimethylaminopyrrolidin-1-yl]-4-methoxyphenyl}prop-2-enamide

HRID 1842617
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HRID 1842617 반응식
[C:1](Cl)(=[O:4])[CH:2]=[CH2:3].[Cl:6][C:7]1[C:8]([C:31]2[CH:32]=[N:33][N:34]3[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=23)=[N:9][C:10]([NH:13][C:14]2[C:19]([O:20][CH3:21])=[CH:18][C:17]([N:22]3[CH2:26][CH2:25][C@@H:24]([N:27]([CH3:29])[CH3:28])[CH2:23]3)=[C:16]([NH2:30])[CH:15]=2)=[N:11][CH:12]=1.CCN(C(C)C)C(C)C>C(Cl)Cl>[Cl:6][C:7]1[C:8]([C:31]2[CH:32]=[N:33][N:34]3[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=23)=[N:9][C:10]([NH:13][C:14]2[C:19]([O:20][CH3:21])=[CH:18][C:17]([N:22]3[CH2:26][CH2:25][C@@H:24]([N:27]([CH3:29])[CH3:28])[CH2:23]3)=[C:16]([NH:30][C:1](=[O:4])[CH:2]=[CH2:3])[CH:15]=2)=[N:11][CH:12]=1
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참가 물질

5

반응물 3

HCID 13140Acryloyl chlorideHCID 81531DiisopropylethylamineHCID 86677235N-(5-Chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)-4-[(3R)-3-dimethylaminopyrrolidin-1-yl]-6-methoxybenzene-1,3-diamine2회

생성물 1

HCID 86677234N-{5-[(5-Chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)amino]-2-[(3R)-3-dimethylaminopyrrolidin-1-yl]-4-methoxyphenyl}prop-2-enamide수율 58%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

A solution of acryloyl chloride (0.042 mL, 0.51 mmol) in CH2Cl2 (1 mL) was added dropwise to a mixture of N-(5-chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)-4-[(3R)-3-dimethylamino-pyrrolidin-1-yl]-6-methoxybenzene-1,3-diamine (Intermediate 18, 245 mg, 0.51 mmol) and DIPEA (0.097 mL, 0.56 mmol) in CH2Cl2 (10 mL), which was cooled in an ice/water bath. The mixture was stirred for 2 h and then washed with brine, dried (Na2SO4) and concentrated in vacuo. Purification by FCC, eluting with 2% 7N methanolic ammonia in CH2Cl2 gave a foam after concentration in vacuo. This foam was triturated using CH2Cl2 and diethyl ether, and the resulting solid was collected by filtration and dried to give the title compound (157 mg, 58%) as a yellow solid; 1H NMR: 1.68-1.83 (1H, m), 2.05-2.16 (1H, m), 2.18 (6H, s), 2.64-2.76 (1H, m), 3.18-3.29 (3H, m), 3.36-3.47 (1H, m), 3.77 (3H, s), 5.67 (1H, dd), 6.16 (1H, dd), 6.48 (1H, dd), 6.54 (1H, s), 7.12 (1H, t), 7.37 (1H, t), 7.43 (1H, s), 8.28-8.46 (2H, m), 8.55 (1H, s), 8.83 (1H, d), 8.94 (1H, s), 9.37 (1H, s); m/z: ES+ MH+ 533.5.

후처리

  1. temperaturewas cooled in an ice/water bath
  2. washwashed with brine
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customPurification by FCC
  6. washeluting with 2% 7N methanolic ammonia in CH2Cl2
  7. customgave a foam
  8. concentrationafter concentration in vacuo
  9. customThis foam was triturated
  10. filtrationthe resulting solid was collected by filtration
  11. customdried

출처 및 근거

ORD 기록
ord-8c3b74886ec1417cbc64dc5fe142932a
출처 데이터셋
uspto-grants-2015_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08946235B2

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