Sodium borohydride → 6-tert-butyl-8-fluoro-2-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(3S)-3-methylmorpholine-4-carbonyl]-2-pyridyl]amino]-6-oxo-3-pyridyl]-2-pyridyl]phthalazin-1-one

HRID 407740Notes

Reaction equation

HRID 407740 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]([C:38]([N:40]5[CH2:45][CH2:44][O:43][CH2:42][C@@H:41]5[CH3:46])=[O:39])=[CH:34][N:33]=4)[C:28](=[O:47])[N:27]([CH3:48])[CH:26]=3)[C:18]=1[CH:19]=[O:20])[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2].[BH4-].[Na+]>CO.ClCCl>[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]([C:38]([N:40]5[CH2:45][CH2:44][O:43][CH2:42][C@@H:41]5[CH3:46])=[O:39])=[CH:34][N:33]=4)[C:28](=[O:47])[N:27]([CH3:48])[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 86684010(S)-2-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(1-methyl-5-(5-(3-methylmorpholine-4-carbonyl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)nicotinaldehyde

Product 1

HCID 866840126-tert-butyl-8-fluoro-2-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(3S)-3-methylmorpholine-4-carbonyl]-2-pyridyl]amino]-6-oxo-3-pyridyl]-2-pyridyl]phthalazin-1-oneYield 29.1%

Reagents, catalysts & solvents 1

HCID 21226129Dichloromethane methanolSolvent

Procedure

A solution of 136d (140 mg, 0.21 mmol) in methanol/dichloromethane (4/4 mL) was added NaBH4 (16 mg, 0.63 mmol). The mixture was stirred at room temperature for 1 h and quenched with water (2 mL). It was then evaporated under reduced pressure and the residue was purified by reverse-phase prep-HPLC to afford 136 (40 mg, 28%) as a white solid. MS-ESI: [M+H]+ 654.3. 1H NMR (500 MHz, DMSO-d6) δ 9.00 (s, 1H), 8.77 (d, J=8.0 Hz, 1H), 8.57 (d, J=5.0 Hz, 1H), 8.53 (d, J=2.5 Hz, 1H), 8.25 (d, J=2.5 Hz, 1H), 7.90 (d, J=1.5 Hz, 1H), 7.78 (d, J=1.0 Hz, 1H), 7.65-7.63 (m, 1H), 7.59 (d, J=2.5 Hz, 1H), 7.53 (d, J=5.0 Hz, 1H), 7.37 (d, J=8.5 Hz, 1H), 4.91-4.89 (m, 1H), 4.45-4.39 (m, 2H), 4.17-4.13 (m, 1H), 3.79-3.67 (m, 2H), 3.58-3.53 (m, overlap, 5H), 3.41-3.36 (m, 1H), 3.29-3.25 (m, 1H), 1.39 (s, 9H), 1.22 (d, J=7.5 Hz, 3H).

Workup

  1. customquenched with water (2 mL)
  2. customIt was then evaporated under reduced pressure
  3. customthe residue was purified by reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-90b9cb9ba32c4d95b0212df75da71df2
Source dataset
uspto-grants-2014_06
Patent number
US08754077B2

Reaction notes

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