Methanol → 2-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2S)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]-2-pyridyl]amino]-6-oxo-3-pyridyl]-2-pyridyl]-5,6,7,8-tetrahydro-1H-pyrrolo[3,4-b]indolizin-3-one

HRID 592961노트

반응식

HRID 592961 반응식
[CH3:1][N:2]1[C:7](=[O:8])[C:6]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([N:16]3[CH2:21][CH2:20][N:19]([CH:22]4[CH2:25][O:24][CH2:23]4)[CH2:18][CH:17]3[CH3:26])=[CH:12][N:11]=2)=[CH:5][C:4]([C:27]2[C:32]([CH:33]=[O:34])=[C:31]([N:35]3[CH2:46][C:45]4[N:44]5[C:39]([CH2:40][CH2:41][CH2:42][CH2:43]5)=[CH:38][C:37]=4[C:36]3=O)[N:30]=[CH:29][CH:28]=2)=[CH:3]1.[BH4-].[Na+].C[OH:51]>>[OH:34][CH2:33][C:32]1[C:31]([N:35]2[C:46](=[O:51])[C:45]3[N:44]4[C:39]([CH2:40][CH2:41][CH2:42][CH2:43]4)=[CH:38][C:37]=3[CH2:36]2)=[N:30][CH:29]=[CH:28][C:27]=1[C:4]1[CH:5]=[C:6]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([N:16]3[CH2:21][CH2:20][N:19]([CH:22]4[CH2:23][O:24][CH2:25]4)[CH2:18][C@@H:17]3[CH3:26])=[CH:12][N:11]=2)[C:7](=[O:8])[N:2]([CH3:1])[CH:3]=1

참가 물질

4

반응물 3

HCID 887MethanolHCID 4311764Sodium borohydrideHCID 866844534-(1-methyl-5-(5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-yl-amino)-6-oxo-1,6-dihydropyridin-3-yl)-2-(1-oxo-5,6,7,8-tetrahydro-1H-pyrrolo[3,4-b]indolizin-2(3H)-yl)nicotinaldehyde

생성물 1

HCID 866844542-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2S)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]-2-pyridyl]amino]-6-oxo-3-pyridyl]-2-pyridyl]-5,6,7,8-tetrahydro-1H-pyrrolo[3,4-b]indolizin-3-one수율 66%

실험 절차

A 25-mL single-neck round-bottomed flask equipped with a magnetic stirrer was charged with 238f (90 mg, 1.0 eq., 0.14 mmol), NaBH4 (23 mg, 5 eq., 0.60 mmol), and methanol (5 mL). The resulting mixture was stirred at room temperature for 20 minutes and quenched with water. It was then concentrated under reduced pressure and the residue was purified by reverse-phase prep-HPLC to afford 238 (60 mg, 66%) as a white solid. MS-ESI: [M+H]+ 637.3. 1H NMR (500 MHz, CDCl3) δ 8.69 (d, J=1.5 Hz, 1H), 8.47 (d, J=5.0 Hz, 1H), 7.99 (d, J=2.5 Hz, 1H), 7.93 (d, J=2.0 Hz, 1H), 7.86 (s, 1H), 7.36-7.31 (m, 2H), 6.83 (d, J=9.0 Hz, 1H), 6.15 (s, 1H), 5.71 (t, J=6.5 Hz, 1H), 4.96 (s, 2H), 4.72-4.63 (m, 4H), 4.52-4.51 (m, 2H), 3.97-3.95 (m, 2H), 3.75 (s, 3H), 3.55-3.53 (m, 1H), 3.48-3.46 (m, 1H), 3.10-3.08 (m, 2H), 2.91-2.89 (m, 2H), 2.58-2.56 (m, 1H), 2.49-2.48 (m, 2H), 2.23-2.19 (m, 1H), 2.08-2.02 (m, 2H), 1.93-1.89 (m, 2H), 1.00 (d, J=6.0 Hz, 3H).

후처리

  1. customA 25-mL single-neck round-bottomed flask equipped with a magnetic stirrer
  2. customquenched with water
  3. concentrationIt was then concentrated under reduced pressure
  4. customthe residue was purified by reverse-phase prep-HPLC

출처 및 근거

ORD 기록
ord-c1e2d72ca9de490eb01cfb2d1d705286
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09238655B2

반응 노트

불러오는 중…