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2,6-Lutidine → 3-[7-chloro-1-[(3S)-1-prop-2-enoylpyrrolidin-3-yl]oxyisoquinolin-3-yl]-1,4-dihydro-1,2,4-triazol-5-one

HRID 1476885
ノート
印刷プレビュー

反応式

HRID 1476885 の反応式
[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([C:18]3[NH:22][C:21](=[O:23])[NH:20][N:19]=3)[N:8]=[C:9]2[O:12][C@H:13]2[CH2:17][CH2:16][NH:15][CH2:14]2)=[CH:4][CH:3]=1.CC1C=CC=C(C)N=1.[C:32](Cl)(=[O:35])[CH:33]=[CH2:34]>C(Cl)Cl>[C:32]([N:15]1[CH2:16][CH2:17][C@H:13]([O:12][C:9]2[C:10]3[C:5](=[CH:4][CH:3]=[C:2]([Cl:1])[CH:11]=3)[CH:6]=[C:7]([C:18]3[NH:22][C:21](=[O:23])[NH:20][N:19]=3)[N:8]=2)[CH2:14]1)(=[O:35])[CH:33]=[CH2:34]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 79372,6-LutidineHCID 13140Acryloyl chlorideHCID 136596960(S)-3-(7-chloro-1-(pyrrolidin-3-yloxy)isoquinolin-3-yl)-1H-1,2,4-triazol-5(4H)-one

生成物 1

HCID 1362950683-[7-chloro-1-[(3S)-1-prop-2-enoylpyrrolidin-3-yl]oxyisoquinolin-3-yl]-1,4-dihydro-1,2,4-triazol-5-one収率 18.6%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane
溶媒

反応条件

温度
0 °C

実験手順

To a mixture of (S)-3-(7-chloro-1-(pyrrolidin-3-yloxy)isoquinolin-3-yl)-1H-1,2,4-triazol-5(4H)-one (180 mg, 0.489 mmol) in DCM (10 mL) was added 2,6-dimethylpyridine (157 mg, 1.467 mmol) at −20° C. followed by the dropwise addition of acryloyl chloride (88 mg, 0.978 mmol, 10 mg/mL in dry DCM). The reaction mixture was warmed to 0° C. over a 30 minute period. The reaction was quenched with MeOH (5 mL) and the mixture concentrated in vacuo. The crude product was purified by preparative HPLC to give the title compound (35 mg, 18%). 1H NMR (400 MHz, DMSO-d6) δ ppm 12.06 (br, 1H), 11.84 (s, 1H), 8.16 (s, 1H), 8.09 (dd, J=1.8 Hz and 8.9 Hz, 1H), 8.03 (s, 1H), 7.83-7.86 (m, 1H), 6.55-6.72 (m, 1H), 6.12-6.19 (m, 2H), 5.63-5.72 (m, 1H), 4.65-4.12 (m, 4H), 2.25-2.42 (m, 2H).

後処理

  1. customThe reaction was quenched with MeOH (5 mL)
  2. concentrationthe mixture concentrated in vacuo
  3. customThe crude product was purified by preparative HPLC

出典と根拠

ORDレコード
ord-e148cc3f82bf4568be73c0b6570942dd
出典データセット
uspto-grants-2016_08
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09402841B2

反応ノート

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