Sodium borohydride → (S)-2-(3-(hydroxymethyl)-4-(1-methyl-5-(5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)pyridin-2-yl)-6,7,8,9-tetrahydropyrazino[1,2-a]indol-1(2H)-one

HRID 1411689Notes

Reaction equation

HRID 1411689 reaction equation
[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][C@@H: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[CH:47]=[CH:46][N:38]4[C:39]5[CH2:40][CH2:41][CH2:42][CH2:43][C:44]=5[CH:45]=[C:37]4[C:36]3=[O:48])[N:30]=[CH:29][CH:28]=2)=[CH:3]1.[BH4-].[Na+]>CO>[OH:34][CH2:33][C:32]1[C:31]([N:35]2[CH:47]=[CH:46][N:38]3[C:39]4[CH2:40][CH2:41][CH2:42][CH2:43][C:44]=4[CH:45]=[C:37]3[C:36]2=[O:48])=[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[CH2:25][O:24][CH2:23]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

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 86684313(S)-4-(1-Methyl-5-(5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)-2-(1-oxo-6,7,8,9-tetrahydropyrazino[1,2-a]indol-2(1H)-yl)nicotinaldehyde

Product 1

HCID 86684314(S)-2-(3-(hydroxymethyl)-4-(1-methyl-5-(5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)pyridin-2-yl)-6,7,8,9-tetrahydropyrazino[1,2-a]indol-1(2H)-oneYield 28%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 176a (200 mg, 0.31 mmol), NaBH4 (47 mg, 1.20), and methanol (10 mL) was stirred at room temperature for 1 h. The reaction mixture was then quenched with water (10 mL) and concentrated under reduced pressure. The residue was extracted with dichloromethane (2×10 mL). The combined dichloromethane extract was concentrated under reduced pressure and the residue was purified with reverse-phase prep-HPLC to afford 176 (42 mg, 28%). MS-ESI: [M+H]+ 649.3. 1H NMR (500 MHz, DMSO-d6) δ 8.66 (d, J=2.5 Hz, 1H), 8.56 (d, J=5.5 Hz, 1H), 8.47 (s, 1H), 7.84 (d, J=2.5 Hz, 1H), 7.50-7.48 (m, 2H), 7.39-7.36 (m, 1H), 7.26-7.24 (m, 2H), 6.83-6.80 (m, 2H), 4.57-4.54 (m, 2H), 4.48-4.40 (m, 3H), 4.35-4.33 (m, 1H), 3.69-3.67 (m, 1H), 3.60 (s, 3H), 3.41-3.38 (m, 2H), 3.11-3.08 (m, 1H), 2.97-2.93 (m, 1H), 2.76-2.74 (m, 2H), 2.62-2.60 (m, 2H), 2.52-2.51 (m, 1H), 2.35-2.32 (m, 2H), 2.19-2.17 (m, 1H), 1.90-1.87 (m, 2H), 1.77-1.75 (m, 2H), 0.94 (d, J=6.5 Hz, 3H).

Workup

  1. customThe reaction mixture was then quenched with water (10 mL)
  2. concentrationconcentrated under reduced pressure
  3. extractionThe residue was extracted with dichloromethane (2×10 mL)
  4. extractionThe combined dichloromethane extract
  5. concentrationwas concentrated under reduced pressure
  6. customthe residue was purified with reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-eb3acca4f10c45dc8e0d02d038bf305a
Source dataset
uspto-grants-2014_12
Patent number
US08921353B2

Reaction notes

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