Methanol → 5-[2-(3,4,6,7,8,9-hexahydro-1H-pyrazino[1,2-a]indol-2-yl)-3-(hydroxymethyl)-4-pyridyl]-1-methyl-3-[[5-[(2S)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]-2-pyridyl]amino]pyridin-2-one

HRID 592906ノート

反応式

HRID 592906 の反応式
[CH2:1]1[C:6]2=[CH:7][C:8]3[CH2:9][CH2:10][CH2:11][CH2:12][C:13]=3[N:5]2[CH2:4][CH2:3][N:2]1[C:14]1[N:21]=[CH:20][CH:19]=[C:18]([C:22]2[CH:27]=[C:26]([NH:28][C:29]3[CH:34]=[CH:33][C:32]([N:35]4[CH2:40][CH2:39][N:38]([CH:41]5[CH2:44][O:43][CH2:42]5)[CH2:37][C@@H:36]4[CH3:45])=[CH:31][N:30]=3)[C:25](=[O:46])[N:24]([CH3:47])[CH:23]=2)[C:15]=1[CH:16]=[O:17].[BH4-].[Na+].CO>ClCCl>[CH2:1]1[C:6]2=[CH:7][C:8]3[CH2:9][CH2:10][CH2:11][CH2:12][C:13]=3[N:5]2[CH2:4][CH2:3][N:2]1[C:14]1[C:15]([CH2:16][OH:17])=[C:18]([C:22]2[CH:27]=[C:26]([NH:28][C:29]3[CH:34]=[CH:33][C:32]([N:35]4[CH2:40][CH2:39][N:38]([CH:41]5[CH2:42][O:43][CH2:44]5)[CH2:37][C@@H:36]4[CH3:45])=[CH:31][N:30]=3)[C:25](=[O:46])[N:24]([CH3:47])[CH:23]=2)[CH:19]=[CH:20][N:21]=1

参加物

5

反応物 3

HCID 887MethanolHCID 4311764Sodium borohydrideHCID 86684407(S)-2-(3,4,6,7,8,9-Hexahydropyrazino[1,2-a]indol-2(1H)-yl)-4-(1-methyl-5-(5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)nicotinaldehyde

生成物 1

HCID 866844095-[2-(3,4,6,7,8,9-hexahydro-1H-pyrazino[1,2-a]indol-2-yl)-3-(hydroxymethyl)-4-pyridyl]-1-methyl-3-[[5-[(2S)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]-2-pyridyl]amino]pyridin-2-one収率 10.5%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

A 50-mL single-neck round-bottomed flask was charged with 220b (100 mg, 1.0 eq., 0.15 mmol), NaBH4 (30 mg, 5.0 eq., 0.75 mmol), methanol (5 mL), and dichloromethane (5 mL). The mixture was stirred at 0° C. for 10 min and quenched with water (5 mL). It was then filtered and the filtrate was concentrated under reduced pressure. The residue was purified by reverse-phase prep-HPLC to afford the title compound (10 mg, 10%). MS-ESI: [M+H]+ 637.5. 1H NMR (500 MHz, DMSO-d6) δ 8.61 (d, J=2.0 Hz, 1H), 8.44 (s, 1H), 8.24 (d, J=5.0 Hz, 1H), 7.82 (d, J=3.0 Hz, 1H), 7.53 (d, J=2.0 Hz, 1H), 7.39-7.36 (m, 1H), 7.24 (d, J=9.0 Hz, 1H), 6.99 (d, J=5.0 Hz, 1H), 5.55 (s, 1H), 5.36-5.35 (m, 1H), 4.57-4.54 (m, 2H), 4.48-4.40 (m, 6H), 3.92-3.90 (m, 2H), 3.79-3.67 (m, 3H), 3.59 (s, 3H), 3.40-3.37 (m, 2H), 3.09-3.07 (m, 1H), 2.95-2.92 (m, 1H), 2.55-2.51 (m, 2H), 2.38-2.30 (m, 4H), 2.17-2.16 (m, 1H), 1.75-1.74 (m, 2H), 1.68-1.65 (m, 2H), 0.92 (d, J=6.5 Hz, 3H).

後処理

  1. customquenched with water (5 mL)
  2. filtrationIt was then filtered
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. customThe residue was purified by reverse-phase prep-HPLC

出典と根拠

ORDレコード
ord-8328a92944f64e2dafda95e146fa0d8e
出典データセット
uspto-grants-2016_01
特許番号
US09238655B2

反応ノート

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