Sodium borohydride → 6-Tert-butyl-2-[4-[5-[(5-ethylisoxazol-3-yl)amino]-1-methyl-6-oxo-3-pyridyl]-3-(hydroxymethyl)-2-pyridyl]-8-fluoro-phthalazin-1-one

HRID 407819Notes

Reaction equation

HRID 407819 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:36]=[C:35]([CH2:37][CH3:38])[O:34][N:33]=4)[C:28](=[O:39])[N:27]([CH3:40])[CH:26]=3)[C:18]=1[CH:19]=[O:20])[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2].[BH4-].[Na+]>ClCCl.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:36]=[C:35]([CH2:37][CH3:38])[O:34][N:33]=4)[C:28](=[O:39])[N:27]([CH3:40])[CH:26]=3)[CH:22]=[CH:23][N:24]=1)[N:9]=[CH:8]2)([CH3:3])([CH3:2])[CH3:4]

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 866840782-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(5-(5-ethylisoxazol-3-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)nicotinaldehyde

Product 1

HCID 866840806-Tert-butyl-2-[4-[5-[(5-ethylisoxazol-3-yl)amino]-1-methyl-6-oxo-3-pyridyl]-3-(hydroxymethyl)-2-pyridyl]-8-fluoro-phthalazin-1-oneYield 37%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 158c (190 mg, 0.35 mmol) in dichloromethane (5 mL) and methanol (5 mL) was added NaBH4 (26.5 mg, 0.70 mmol). The reaction mixture was stirred at room temperature for 1 h and quenched with aqueous NH4Cl. It was then concentrated under reduced pressure and the residue was extracted with dichloromethane. The combined extract was washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by reverse-phase prep-HPLC to afford 158 (70 mg, 37%) as white solid. MS-ESI: [M+H]+ 545.3. 1H NMR (500 MHz, DMSO-d6) δ 9.01 (s, 1H), 8.58 (d, J=5.0 Hz, 1H), 8.54 (d, J=2.0 Hz, 1H), 8.01 (d, J=2.0 Hz, 1H), 7.90 (s, 1H), 7.79 (d, J=13 Hz, 1H), 7.57 (d, J=2.5 Hz, 1H), 7.51 (d, J=5.0 Hz, 1H), 6.26 (s, 1H), 4.90 (s, 1H), 4.44-4.43 (m, 2H), 3.61 (s, 3H), 2.69-2.65 (m, 2H), 1.40 (s, 9H), 1.19 (t, J=8.0 Hz, 3H)

Workup

  1. customquenched with aqueous NH4Cl
  2. concentrationIt was then concentrated under reduced pressure
  3. extractionthe residue was extracted with dichloromethane
  4. extractionThe combined extract
  5. washwas washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-e61bc7f9453d491ab07f75ea71e23813
Source dataset
uspto-grants-2014_06
Patent number
US08754077B2

Reaction notes

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