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

HRID 1842647노트

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HRID 1842647 반응식
[C:1](Cl)(=[O:4])[CH:2]=[CH2:3].[NH2:6][C:7]1[C:8]([N:33]([CH2:35][CH2:36][N:37]([CH3:39])[CH3:38])[CH3:34])=[CH:9][C:10]([O:31][CH3:32])=[C:11]([NH:13][C:14]2[N:19]=[C:18]([C:20]3[CH:21]=[N:22][N:23]4[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=34)[C:17]([C:29]#[N:30])=[CH:16][N:15]=2)[CH:12]=1.CCN(C(C)C)C(C)C>C1COCC1>[C:29]([C:17]1[C:18]([C:20]2[CH:21]=[N:22][N:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=23)=[N:19][C:14]([NH:13][C:11]2[C:10]([O:31][CH3:32])=[CH:9][C:8]([N:33]([CH2:35][CH2:36][N:37]([CH3:38])[CH3:39])[CH3:34])=[C:7]([NH:6][C:1](=[O:4])[CH:2]=[CH2:3])[CH:12]=2)=[N:15][CH:16]=1)#[N:30]

참가 물질

5

반응물 3

HCID 13140Acryloyl chlorideHCID 81531DiisopropylethylamineHCID 866772852-{[5-Amino-4-(2-dimethylaminoethyl-methylamino)-2-methoxyphenyl]-amino}-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidine-5-carbonitrile2회

생성물 1

HCID 86677284N-{5-[(5-Cyano-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)amino]-2-[2-dimethylaminoethyl-methylamino]-4-methoxyphenyl}prop-2-enamide수율 60%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
0 °C

실험 절차

A solution of acryloyl chloride (0.087 mL, 1M, THF, 0.09 mmol) was added dropwise to a mixture of 2-{[5-amino-4-(2-dimethylaminoethyl-methylamino)-2-methoxyphenyl]-amino}-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidine-5-carbonitrile (Intermediate 121, 0.036 g, 0.08 mmol) and DIPEA (0.017 mL, 0.09 mmol) in THF (5 mL) which was cooled to 0° C. The mixture was stirred at 0° C. for 3 h, then concentrated in vacuo. Purification by FCC, eluting with 0-20% CH3OH in CH2Cl2 have crude product which appeared to contain the hydrochloride salt of DIPEA. The material was dissolved in CH2Cl2 (10 mL) and stirred with sat. NaHCO3 solution (10 mL). The phases were separated and the organic solution was concentrated in vacuo to give the title compound (24 mg, 60%) as a yellow gum; 1H NMR: (CDCl3) 2.22 (6H, s), 2.26 (2H, dd), 2.67 (3H, d), 2.77-2.86 (2H, m), 3.81 (3H, s), 5.61 (1H, dd), 6.16-6.35 (2H, m), 6.76 (1H, s), 6.88 (1H, d), 7.23 (1H, s), 7.65 (1H, s), 8.50 (2H, dd), 8.59 (1H, s), 9.02 (1H, s), 9.28 (1H, s), 10.08 (1H, s); m/z: ES+ MH+ 512.29.

후처리

  1. concentrationconcentrated in vacuo
  2. customPurification by FCC
  3. washeluting with 0-20% CH3OH in CH2Cl2
  4. dissolutionThe material was dissolved in CH2Cl2 (10 mL)
  5. stirringstirred with sat. NaHCO3 solution (10 mL)
  6. customThe phases were separated
  7. concentrationthe organic solution was concentrated in vacuo

출처 및 근거

ORD 기록
ord-c59d80d28cd5408f8ed2490a9ab4e7c9
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08946235B2

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