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 1411845노트

반응식

HRID 1411845 반응식
[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

참가 물질

5

반응물 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

생성물 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-one수율 10.5%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

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온도
0 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-8835b47b94354bc88e1fde228f90ba4b
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08921353B2

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