Sodium borohydride → 6-tert-Butyl-2-(4-(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)-3-(hydroxymethyl)pyridin-2-yl)-8-fluorophthalazin-1(2H)-one

HRID 407632Notes

Reaction equation

HRID 407632 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][C@@H:42]([CH3:44])[N:41]([CH:45]6[CH2:48][O:47][CH2:46]6)[CH2:40][C@@H:39]5[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][C@@H:42]([CH3:44])[N:41]([CH:45]6[CH2:48][O:47][CH2:46]6)[CH2:40][C@@H:39]5[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)([CH3:2])([CH3:3])[CH3:4]

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 866839282-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(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)nicotinaldehyde

Product 1

HCID 715538656-tert-Butyl-2-(4-(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)-3-(hydroxymethyl)pyridin-2-yl)-8-fluorophthalazin-1(2H)-oneYield 80%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
30 °C

Procedure

A mixture of 110a (100 mg, 0.15 mmol) and NaBH4 (20 mg, 0.45 mmol) in MeOH (30 mL) was stirred at 30° C. for 2 h. The mixture was quenched with water and extracted with EtOAc (10 mL×3). The combined EtOAc extract was concentrated under reduced pressure and the residue was purified by reverse-phase prep-HPLC to afford 110 (80 mg, 80%). MS: [M+H]+ 695.3. 1H NMR (500 MHz, CDCl3) δ 8.72 (d, J=2, 1H), 8.67 (d, J=5, 1H), 8.35 (d, J=2.5, 1H), 8.05 (d, J=3, 1H), 7.88 (s, 1H), 7.68 (d, J=2.5, 1H), 7.58-7.55 (m, 3H), 7.38-7.36 (m, 1H), 6.82 (d, J=8.5, 1H), 4.78-4.71 (m, 2H), 4.67-4.61 (m, 2H), 4.50 (s, 2H), 4.07 (t, J=6, 1H), 3.78-3.74 (m, 4H), 3.22-3.20 (m, 1H), 2.92 (d, J=3, 1H), 2.77-2.71 (m, 2H), 2.51-2.48 (m, 1H), 1.20-1.95 (m, 1H), 1.45 (s, 9H), 0.93-0.90 (m, 6H)

Workup

  1. customThe mixture was quenched with water
  2. extractionextracted with EtOAc (10 mL×3)
  3. extractionThe combined EtOAc extract
  4. concentrationwas concentrated under reduced pressure
  5. customthe residue was purified by reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-9113da938de6423d9c715d5f1766ab42
Source dataset
uspto-grants-2014_06
Patent number
US08754077B2

Reaction notes

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