Acryloyl chloride → N-{2-[(3aR,6aR)-5-Methyl-2,3,3a,4,6,6a-hexahydropyrrolo[3,2-c]pyrrol-1-yl]-5-[(5-chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)amino]-4-methoxyphenyl}prop-2-enamide

HRID 1842618

反応式

HRID 1842618 の反応式
[C:1](Cl)(=[O:4])[CH:2]=[CH2:3].[CH3:6][N:7]1[CH2:11][C@@H:10]2[N:12]([C:15]3[CH:20]=[C:19]([O:21][CH3:22])[C:18]([NH:23][C:24]4[N:29]=[C:28]([C:30]5[CH:31]=[N:32][N:33]6[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=56)[C:27]([Cl:39])=[CH:26][N:25]=4)=[CH:17][C:16]=3[NH2:40])[CH2:13][CH2:14][C@@H:9]2[CH2:8]1.CCN(C(C)C)C(C)C>C(Cl)Cl>[CH3:6][N:7]1[CH2:11][C@@H:10]2[N:12]([C:15]3[CH:20]=[C:19]([O:21][CH3:22])[C:18]([NH:23][C:24]4[N:29]=[C:28]([C:30]5[CH:31]=[N:32][N:33]6[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=56)[C:27]([Cl:39])=[CH:26][N:25]=4)=[CH:17][C:16]=3[NH:40][C:1](=[O:4])[CH:2]=[CH2:3])[CH2:13][CH2:14][C@@H:9]2[CH2:8]1

参加物

5

反応物 3

HCID 13140Acryloyl chlorideHCID 81531DiisopropylethylamineHCID 866772374-[(3aR,6aR)-5-methyl-2,3,3a,4,6,6a-hexahydropyrrolo[3,2-c]pyrrol-1-yl]-N-(5-chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)-6-methoxybenzene-1,3-diamine2 回

生成物 1

HCID 86677236N-{2-[(3aR,6aR)-5-Methyl-2,3,3a,4,6,6a-hexahydropyrrolo[3,2-c]pyrrol-1-yl]-5-[(5-chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)amino]-4-methoxyphenyl}prop-2-enamide収率 52.4%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

Acryloyl chloride (1M in THF, 0.225 mL, 0.22 mmol) in CH2Cl2 (1 mL) was added dropwise to a mixture of 4-[(3aR,6aR)-5-methyl-2,3,3a,4,6,6a-hexahydropyrrolo[3,2-c]pyrrol-1-yl]-N-(5-chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)-6-methoxybenzene-1,3-diamine (Intermediate 35, 105 mg, 0.21 mmol) and DIPEA (0.041 mL, 0.24 mmol) in CH2Cl2 (3 mL), which was cooled in an ice/water bath. The mixture was stirred for 0.5 h, washed with brine and then concentrated in vacuo. Purification by FCC, eluting with 0-2.5% 7N methanolic ammonia in CH2Cl2 gave the title compound (60 mg, 52%) as a pale yellow solid; 1H NMR: 1.77-1.81 (1H, m), 1.95-2.16 (5H, m), 2.24-2.35 (1H, m), 2.38-2.48 (1H, m), 2.86-2.90 (1H, m), 3.18-3.22 (1H, m), 3.37-3.45 (1H, m), 3.76 (3H, s), 4.33-4.37 (1H, m), 5.68 (1H, dd), 6.18 (1H, dd), 6.51 (1H, dd), 6.66 (1H, s), 7.10 (1H, dt), 7.33-7.41 (1H, m), 7.65 (1H, s), 8.3-8.4 (2H, m), 8.56 (1H, s), 8.81 (1H, d), 8.94 (1H, s), 9.38 (1H, s); m/z: ES+, MH+ 545.57.

後処理

  1. temperaturewas cooled in an ice/water bath
  2. washwashed with brine
  3. concentrationconcentrated in vacuo
  4. customPurification by FCC
  5. washeluting with 0-2.5% 7N methanolic ammonia in CH2Cl2

出典と根拠

ORDレコード
ord-db05f467cb2f4eb1834038fc39253dd9
出典データセット
uspto-grants-2015_02
特許番号
US08946235B2

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