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

HRID 1185043Notes

Reaction equation

HRID 1185043 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][C@@H:43]([CH3:45])[N:42]([CH:46]6[CH2:49][O:48][CH2:47]6)[CH2:41][C@@H:40]5[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][C@@H:43]([CH3:45])[N:42]([CH:46]6[CH2:49][O:48][CH2:47]6)[CH2:41][C@@H:40]5[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)([CH3:3])([CH3:4])[CH3:2]

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 866839232-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(5-(5-((2S,5R)-2,5-dimethyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-4-fluorobenzaldehyde

Product 1

HCID 866839246-tert-Butyl-2-(3-(5-(5-((2S,5R)-2,5-dimethyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-5-fluoro-2-(hydroxymethyl)phenyl)-8-fluorophthalazin-1(2H)-oneYield 22.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

At 0° C., to a solution of 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(5-(5-((2S,5R)-2,5-dimethyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-4-fluorobenzaldehyde 108a (54 mg, 0.076 mmol) in methanol (5 mL) was added sodium borohydride (9.0 mg, 0.23 mmol). The mixture was stirred for 60 minutes. It was then quenched with water (1.0 mL) and concentrated under reduced pressure. The residue was purified by reverse-phase prep-HPLC to afford 108 (12 mg, 22%). MS: [M+H]+ 712.3. 1H NMR (500 MHz, CDCl3) δ 8.63 (d, J=2.5 Hz, 1H), 8.31 (d, J=2.0 Hz, 1H), 8.05 (d, J=2.5 Hz, 1H), 7.87 (s, 1H), 7.58-7.55 (m, 2H), 7.44 (d, J=2.0 Hz, 1H), 7.36 (s, 1H), 7.30 (d, J=2.0 Hz, 1H), 7.12 (dd, J=2.5, 8.5 Hz, 1H), 6.82 (d, J=8.5 Hz, 1H), 4.76-4.73 (m, 2H), 4.68-4.61 (m, 2H), 4.38-4.36 (m, 2H), 3.74-3.72 (m, 2H), 3.72 (s, 3H), 3.22-3.20 (m, 1H), 2.94-2.92 (m, 1H), 2.74-2.72 (m, 2H), 2.50-2.48 (m, 1H), 1.98-1.96 (m, 1H), 1.45 (s, 9H), 0.93-0.91 (m, 6H).

Workup

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

Sources & evidence

ORD record
ord-df039df65bfb4688966f64985c9764d1
Source dataset
uspto-grants-2014_03
Patent number
US08669251B2

Reaction notes

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