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

HRID 1026490

Reaction equation

HRID 1026490 reaction equation
[CH2:1]([C@H:3]1[CH2:8][N:7]([CH:9]2[CH2:12][O:11][CH2:10]2)[CH2:6][CH2:5][N:4]1[C:13]1[CH:14]=[CH:15][C:16]([NH:19][C:20]2[C:25](=[O:26])[N:24]([CH3:27])[CH:23]=[C:22]([C:28]3[CH:35]=[C:34]([F:36])[CH:33]=[C:32]([N:37]4[CH:49]=[CH:48][N:40]5[C:41]6[CH2:42][CH2:43][CH2:44][CH2:45][C:46]=6[CH:47]=[C:39]5[C:38]4=[O:50])[C:29]=3[CH:30]=[O:31])[CH:21]=2)=[N:17][CH:18]=1)[CH3:2].[BH4-].[Na+]>CO>[CH2:1]([C@H:3]1[CH2:8][N:7]([CH:9]2[CH2:10][O:11][CH2:12]2)[CH2:6][CH2:5][N:4]1[C:13]1[CH:14]=[CH:15][C:16]([NH:19][C:20]2[C:25](=[O:26])[N:24]([CH3:27])[CH:23]=[C:22]([C:28]3[C:29]([CH2:30][OH:31])=[C:32]([N:37]4[CH:49]=[CH:48][N:40]5[C:41]6[CH2:42][CH2:43][CH2:44][CH2:45][C:46]=6[CH:47]=[C:39]5[C:38]4=[O:50])[CH:33]=[C:34]([F:36])[CH:35]=3)[CH:21]=2)=[N:17][CH:18]=1)[CH3:2]

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 86683758(S)-2-(5-(5-(2-Ethyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-4-fluoro-6-(1-oxo-6,7,8,9-tetrahydropyrazino[1,2-a]indol-2(1H)-yl)benzaldehyde

Product 1

HCID 77844703(S)-2-(3-(5-(5-(2-ethyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-5-fluoro-2-(hydroxymethyl)phenyl)-6,7,8,9-tetrahydropyrazino[1,2-a]indol-1(2H)-oneYield 31.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
25 °C

Procedure

A mixture of 122b (100 mg, 0.15 mmol), NaBH4 (22 mg, 0.60), and methanol (10 mL) was stirred at 25° C. for 1 h. It was then quenched with water (5 mL) and concentrated under reduced pressure. The residue was extracted with dichloromethane (2×10 mL) and the combined organic layer was concentrated under reduced pressure. The residue was purified by reverse-phase prep-HPLC to afford 122 (32 mg, 31%). MS: [M+H]+ 680.3. 1H NMR (500 MHz, CDCl3) δ 8.56 (s, 1H), 7.91 (s, 1H), 7.80 (s, 1H), 7.53 (s, 1H), 7.28-7.26 (m, 2H), 7.05 (s, 1H), 6.97-6.93 (m, 2H), 6.81 (d, J=8.5 Hz, 1H), 6.45 (d, J=5.5 Hz, 1H), 4.71-4.61 (m, 4H), 4.38 (d, J=12.0 Hz, 1H), 4.36 (d, J=11.5 Hz, 1H), 3.70 (s, 3H), 3.52 (bs, 1H), 3.31 (d, J=5.5 Hz, 1H), 3.13-3.10 (m, 2H), 2.75-2.70 (m, 4H), 2.56-2.43 (m, 4H), 1.98-1.96 (m, 2H), 1.85-1.84 (m, 2H), 1.39-1.36 (m, 2H), 0.82 (t, J=7.0 Hz, 3H).

Workup

  1. customIt was then quenched with water (5 mL)
  2. concentrationconcentrated under reduced pressure
  3. extractionThe residue was extracted with dichloromethane (2×10 mL)
  4. concentrationthe combined organic layer was concentrated under reduced pressure
  5. customThe residue was purified by reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-318a8762db4c49e5b6061d439240cba9
Source dataset
uspto-grants-2014_05
Patent number
US08729072B2

Linked notes

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