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

HRID 407641Notes

Reaction equation

HRID 407641 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[CH2:48][CH3:49])=[CH:34][N:33]=4)[C:28](=[O:50])[N:27]([CH3:51])[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[CH2:48][CH3:49])=[CH:34][N:33]=4)[C:28](=[O:50])[N:27]([CH3:51])[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 86683931(S)-2-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(5-(5-(2-ethyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)nicotinaldehyde

Product 1

HCID 74223957(S)-6-tert-Butyl-2-(4-(5-(5-(2-ethyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-3-(hydroxymethyl)pyridin-2-yl)-8-fluorophthalazin-1(2H)-oneYield 50.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
25 °C

Procedure

A mixture of 112a (140 mg, 0.20 mmol), NaBH4 (21 mg, 0.60) and CH3OH (8 mL) was stirred at 25° C. for 1 h. Then the reaction mixture was quenched with water (10 mL), the mixture was extracted with CH2Cl2 (15 mL×2). The combined CH2Cl2 extract was concentrated under reduced pressure. The residue was purified with reverse-phase prep-HPLC to afford 112 (70 mg, 50%). LCMS: [M+H]+ 695. 1H NMR (500 MHz, DMSO) δ 8.50-8.60 (m, 2H), 8.44 (s, 1H), 7.90 (d, J=1.5, 1H), 7.82 (d, J=3.0, 1H), 7.75-7.78 (m, 1H), 7.51-7.53 (m, 1H), 7.45 (d, J=2.5, 1H), 7.33-7.35 (m, 1H), 7.22-7.24 (m, 1H), 4.47-4.59 (m, 2H), 4.36-4.45 (m, 4H), 3.60 (s, 3H), 3.46-3.50 (m, 1H), 3.38-3.41 (m, 3H), 3.14-3.17 (m, 1H), 2.96-3.00 (m, 1H), 2.60-2.64 (m, 1H), 2.50-2.55 (m, 1H), 2.14-2.17 (m, 1H), 2.06-2.10 (m, 1H), 1.66-1.69 (m, 1H), 1.39 (s, 9H), 1.21-1.28 (m, 1H), 0.77-0.80 (m, 3H)

Workup

  1. customThen the reaction mixture was quenched with water (10 mL)
  2. extractionthe mixture was extracted with CH2Cl2 (15 mL×2)
  3. extractionThe combined CH2Cl2 extract
  4. concentrationwas concentrated under reduced pressure
  5. customThe residue was purified with reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-6fae3dd9da664f5eb68d6402c6f42c7c
Source dataset
uspto-grants-2014_06
Patent number
US08754077B2

Reaction notes

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