Sodium borohydride → 6-tert-butyl-8-fluoro-2-[3-(hydroxymethyl)-4-[5-[[5-(2-methoxyethyl)-6,7-dihydro-4H-pyrazolo[1,5-a]pyrazin-2-yl]amino]-1-methyl-6-oxo-3-pyridyl]-2-pyridyl]phthalazin-1-one

HRID 407725Notes

Reaction equation

HRID 407725 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:44]=[C:35]5[CH2:36][N:37]([CH2:40][CH2:41][O:42][CH3:43])[CH2:38][CH2:39][N:34]5[N:33]=4)[C:28](=[O:45])[N:27]([CH3:46])[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:44]=[C:35]5[CH2:36][N:37]([CH2:40][CH2:41][O:42][CH3:43])[CH2:38][CH2:39][N:34]5[N:33]=4)[C:28](=[O:45])[N:27]([CH3:46])[CH:26]=3)[CH:22]=[CH:23][N:24]=1)[N:9]=[CH:8]2)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 866839932-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(5-(5-(2-methoxyethyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)nicotinaldehyde

Product 1

HCID 866839956-tert-butyl-8-fluoro-2-[3-(hydroxymethyl)-4-[5-[[5-(2-methoxyethyl)-6,7-dihydro-4H-pyrazolo[1,5-a]pyrazin-2-yl]amino]-1-methyl-6-oxo-3-pyridyl]-2-pyridyl]phthalazin-1-oneYield 27.7%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 133e (180 mg, 0.287 mmol) in dichloromethane (5 mL) and methanol (5 mL) was added NaBH4 (21.7 mg, 0.574 mmol). After stirring at room temperature for 1 h, it was quenched with aqueous NH4Cl (5 mL) and concentrated under reduced pressure. The residue was extracted with dichloromethane (3×20 mL) The combined organic layer was washed with brine, dried over Na2SO4, concentrated under reduced pressure, and purified by reverse-phase prep-HPLC to afford 133 (50 mg, 27%) as a white solid. MS-ESI: [M+H]+ 629.3. 1H NMR (500 MHz, DMSO-d6) δ 8.57 (d, J=5.5 Hz, 1H), 8.54 (d, J=2.5 Hz, 1H), 8.22 (s, 1H), 8.04 (d, J=2.5 Hz, 1H), 7.90 (d, J=1.5 Hz, 1H), 7.78 (dd, J=1.5, 13.5 Hz, 1H), 7.51 (d, J=5.5 Hz, 1H), 7.39 (d, J=2.0 Hz, 1H), 5.89 (s, 1H), 4.90-4.88 (m, 1H), 4.42 (s, 2H), 3.92 (t, J=5.5 Hz, 2H), 3.61 (s, 2H), 3.59 (s, 3H), 3.50 (t, J=5.0 Hz, 2H), 3.25 (s, 3H), 2.90 (t, J=5.5 Hz, 2H), 2.67 (t, J=5.0 Hz, 2H), 1.40 (s, 9H).

Workup

  1. customit was quenched with aqueous NH4Cl (5 mL)
  2. concentrationconcentrated under reduced pressure
  3. extractionThe residue was extracted with dichloromethane (3×20 mL) The combined organic layer
  4. washwas washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. custompurified by reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-d28fe3dd887c449c86499319e8f3593d
Source dataset
uspto-grants-2014_06
Patent number
US08754077B2

Reaction notes

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