Sodium borohydride → 2-{5-[5-((2S,5R)-2,5-Dimethyl-4-oxetan-3-yl-piperazin-1-yl)-pyridin-2-ylamino]-3'-hydroxymethyl-1-methyl-6-oxo-1,6-dihydro-[3,4']bipyridinyl-2'-yl}-2,3,5,6,7,8-hexahydro-4H-2,4b-diaza-fluoren-1-one

HRID 592702Notes

Reaction equation

HRID 592702 reaction equation
[CH3:1][CH:2]1[CH2:7][N:6]([CH:8]2[CH2:11][O:10][CH2:9]2)[CH:5]([CH3:12])[CH2:4][N:3]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:33]([CH:34]=[O:35])=[C:32]([N:36]4[CH2:48][CH2:47][C:46]5[N:45]6[C:40]([CH2:41][CH2:42][CH2:43][CH2:44]6)=[CH:39][C:38]=5[C:37]4=[O:49])[N:31]=[CH:30][CH:29]=3)[CH:21]=2)=[N:17][CH:18]=1.[BH4-].[Na+]>CO>[CH3:1][C@H:2]1[CH2:7][N:6]([CH:8]2[CH2:11][O:10][CH2:9]2)[C@H:5]([CH3:12])[CH2:4][N:3]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:29]=[CH:30][N:31]=[C:32]([N:36]4[CH2:48][CH2:47][C:46]5[N:45]6[C:40]([CH2:41][CH2:42][CH2:43][CH2:44]6)=[CH:39][C:38]=5[C:37]4=[O:49])[C:33]=3[CH2:34][OH:35])[CH:21]=2)=[N:17][CH:18]=1

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 866842764-(5-(5-(2,5-Dimethyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-(1-oxo-3,4,6,7,8,9-hexahydropyrido[3,4-b]indolizin-2(1H)-yl)nicotinaldehyde

Product 1

HCID 866842772-{5-[5-((2S,5R)-2,5-Dimethyl-4-oxetan-3-yl-piperazin-1-yl)-pyridin-2-ylamino]-3'-hydroxymethyl-1-methyl-6-oxo-1,6-dihydro-[3,4']bipyridinyl-2'-yl}-2,3,5,6,7,8-hexahydro-4H-2,4b-diaza-fluoren-1-oneYield 40.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 155b (80 mg, 0.12 mmol) at 0° C. in methanol (5 mL) was added sodium borohydride (12 mg, 0.36 mmol). The reaction mixture was stirred for 30 minutes. It was then quenched with water (1 mL) and concentrated under reduced pressure. The residue was purified by reverse-phase prep-HPLC to afford 155 (32 mg, 40%). MS-ESI: [M+H]+ 665.3. 1H NMR (500 MHz, CDCl3) δ 8.68 (d, J=2.0 Hz, 1H), 8.50 (d, J=5.0 Hz, 1H), 8.04 (d, J=2.5 Hz, 1H), 7.88 (s, 1H), 7.86 (d, J=2.5 Hz, 1H), 7.37-7.33 (m, 2H), 6.82 (d, J=9.0 Hz, 1H), 6.32 (s, 1H), 5.02 (d, J=13.0 Hz, 1H), 4.78-4.71 (m, 2H), 4.67-4.61 (m, 3H), 4.44-4.39 (m, 1H), 4.31-4.29 (m, 1H), 3.96-3.91 (m, 1H), 3.86-3.80 (m, 2H), 3.78-3.75 (m, 1H), 3.72 (s, 3H), 3.21-3.19 (m, 1H), 3.01-2.93 (m, 3H), 2.85-2.83 (m, 2H), 2.72 (d, J=10.0 Hz, 2H), 2.49-2.47 (m, 1H), 2.05-2.03 (m, 2H), 1.98-1.97

Workup

  1. customIt was then quenched with water (1 mL)
  2. concentrationconcentrated under reduced pressure
  3. customThe residue was purified by reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-42fa3d434fda4ea7aa60b39416721d72
Source dataset
uspto-grants-2016_01
Patent number
US09238655B2

Reaction notes

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