Sodium borohydride → (S)-6-tert-Butyl-2-(3-(5-(5-(2-ethyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-yl-amino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-5-fluoro-2-(hydroxymethyl)phenyl)-8-fluorophthalazin-1(2H)-one

HRID 1185053Notes

Reaction equation

HRID 1185053 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[CH:24]=[C:23]([F:25])[CH:22]=[C:21]([C:26]3[CH:31]=[C:30]([NH:32][C:33]4[CH:38]=[CH:37][C:36]([N:39]5[CH2:44][CH2:43][N:42]([CH:45]6[CH2:48][O:47][CH2:46]6)[CH2:41][C@@H:40]5[CH2:49][CH3:50])=[CH:35][N:34]=4)[C:29](=[O:51])[N:28]([CH3:52])[CH:27]=3)[C:18]=1[CH:19]=[O:20])[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2].[BH4-].[Na+]>CO>[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[CH:24]=[C:23]([F:25])[CH:22]=[C:21]([C:26]3[CH:31]=[C:30]([NH:32][C:33]4[CH:38]=[CH:37][C:36]([N:39]5[CH2:44][CH2:43][N:42]([CH:45]6[CH2:46][O:47][CH2:48]6)[CH2:41][C@@H:40]5[CH2:49][CH3:50])=[CH:35][N:34]=4)[C:29](=[O:51])[N:28]([CH3:52])[CH:27]=3)[C:18]=1[CH2:19][OH:20])[N:9]=[CH:8]2)([CH3:2])([CH3:3])[CH3:4]

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 86683930(S)-2-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(5-(5-(2-ethyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-4-fluorobenzaldehyde

Product 1

HCID 89541455(S)-6-tert-Butyl-2-(3-(5-(5-(2-ethyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-yl-amino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-5-fluoro-2-(hydroxymethyl)phenyl)-8-fluorophthalazin-1(2H)-oneYield 32.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 111g (100 mg, 0.14 mmol) at 0° C. in methanol (5 mL) was added sodium borohydride (16.0 mg, 0.42 mmol). The mixture was stirred for 60 minutes. It was then quenched with water (1.0 mL) and concentrated. The residue was purified by reverse-phase prep-HPLC to afford 111 (32 mg, 32%). MS: [M+H]+ 712.3. 1H NMR (500 MHz, CDCl3) δ 8.57 (d, J=2.0 Hz, 1H), 8.30 (d, J=2.0 Hz, 1H), 7.94 (s, 1H), 7.80 (s, 1H), 7.58 (s, 2H), 7.41 (d, J=2.0 Hz, 1H), 7.31-7.28 (m, 2H), 7.12 (dd, J=2.5, 8.5 Hz, 1H), 6.82 (d, J=9.0 Hz, 1H), 4.73-4.70 (m, 4H), 4.37 (s, 2H), 3.74-3.72 (m, 1H), 3.71 (s, 3H), 3.56-3.54 (m, 1H), 3.34-3.32 (m, 1H), 3.15-3.13 (m, 2H), 2.58-2.36 (m, 4H), 1.45 (s, 9H), 1.44-1.43 (m, 2H), 0.83 (t, J=7.5 Hz, 3H).

Workup

  1. customIt was then quenched with water (1.0 mL)
  2. concentrationconcentrated
  3. customThe residue was purified by reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-750a212c527c45379b5f0ec59dcd1a50
Source dataset
uspto-grants-2014_03
Patent number
US08669251B2

Reaction notes

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