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

HRID 407623Notes

Reaction equation

HRID 407623 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[N:24]=[CH:23][CH:22]=[C:21]([C:25]3[CH:30]=[C:29]([NH:31][C:32]4[CH:37]=[CH:36][C:35]([N:38]5[CH2:43][CH2:42][N:41]([CH:44]6[CH2:47][O:46][CH2:45]6)[CH2:40][C@H:39]5[CH3:48])=[CH:34][N:33]=4)[C:28](=[O:49])[N:27]([CH3:50])[CH:26]=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[C:18]([CH2:19][OH:20])=[C:21]([C:25]3[CH:30]=[C:29]([NH:31][C:32]4[CH:37]=[CH:36][C:35]([N:38]5[CH2:43][CH2:42][N:41]([CH:44]6[CH2:47][O:46][CH2:45]6)[CH2:40][C@H:39]5[CH3:48])=[CH:34][N:33]=4)[C:28](=[O:49])[N:27]([CH3:50])[CH:26]=3)[CH:22]=[CH:23][N:24]=1)[N:9]=[CH:8]2)([CH3:3])([CH3:2])[CH3:4]

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 86683920(R)-2-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(1-methyl-5-(5-(2-methyl-4-(oxetan-3-yl)piperazine-1-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)nicotinaldehyde

Product 1

HCID 74223956(R)-6-tert-Butyl-8-fluoro-2-(3-(hydroxymethyl)-4-(1-methyl-5-(5-(2-methyl-4-(oxetan-3-yl)piperazine-1-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)pyridin-2-yl)phthalazin-1(2H)-oneYield 8.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
20 °C

Procedure

A solution of 106b (90.0 mg, 0.13 mmol) in MeOH (10 mL) was added NaBH4 (15.0 mg, 0.39 mmol). The mixture was stirred at 20° C. for 2 h. It was then evaporated and the residue was purified by reverse-phase prep-HPLC to afford 106 (7.3 mg, 8%) as a white solid. LCMS: (M+H)+ 681.4. 1H NMR (500 MHz, DMSO) δ 8.63 (d, J=2.5, 1H), 8.57 (d, J=5.0, 1H), 8.54 (d, J=2.0, 1H), 8.47 (s, 1H), 7.91 (s, 1H), 7.86 (d, J=3.0, 1H), 7.78 (d, J=12.5, 1H), 7.53 (d, J=5.0, 1H), 7.47 (d, J=2.0, 1H), 7.36-7.39 (m, 1H), 7.25 (d, J=9.5, 1H), 4.90 (s, 1H), 4.54-4.58 (m, 2H), 4.47 (t, J=6.0, 1H), 4.39-4.43 (m, 3H), 3.69 (s, 1H), 3.61 (s, 3H), 3.37-3.42 (m, 1H), 3.09-3.11 (m, 1H), 2.95 (t, J=9.0, 1H), 2.54-2.56 (m, 1H), 2.30-2.37 (m, 2H), 2.19 (t, J=8.0, 1H), 1.39 (s, 9H), 0.94-0.93 (d, J=6.5, 3H)

Workup

  1. customIt was then evaporated
  2. customthe residue was purified by reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-dc820acd72fb425f9398272213ef64ef
Source dataset
uspto-grants-2014_06
Patent number
US08754077B2

Reaction notes

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