Sodium borohydride → HCID 71008438, compound

HRID 1025602Notes

Reaction equation

HRID 1025602 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[C:18]([CH:42]=[O:43])=[C:19]([N:23]3[CH:27]=[C:26]([C:28]([NH2:30])=[O:29])[C:25]([NH:31][C:32]4[CH:37]=[CH:36][C:35]([C:38]([OH:41])([CH3:40])[CH3:39])=[CH:34][CH:33]=4)=[N:24]3)[CH:20]=[CH:21][CH:22]=1)[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2].[BH4-].[Na+]>CO.ClCCl.O>[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]([CH2:42][OH:43])=[C:19]([N:23]3[CH:27]=[C:26]([C:28]([NH2:30])=[O:29])[C:25]([NH:31][C:32]4[CH:33]=[CH:34][C:35]([C:38]([OH:41])([CH3:40])[CH3:39])=[CH:36][CH:37]=4)=[N:24]3)[CH:20]=[CH:21][CH:22]=1)[N:9]=[CH:8]2)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 2

HCID 4311764Sodium borohydrideHCID 86673716HCID 86673716, compound

Product 1

HCID 71008438HCID 71008438, compoundYield 91.2%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

1-[3-(6-tert-Butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-2-formyl-phenyl]-3-[4-(1-hydroxy-1-methyl-ethyl)-phenylamino]-1H-pyrazole-4-carboxylic acid amide (34 mg, 0.06 mmol) was dissolved in a solution of 1:1 methanol and dichloromethane (15 ml). To this was added a solution of sodium borohydride (11 mg, 0.29 mmol) dissolved in water (0.25 ml), via drop-wise addition. After 10 minutes stirring the volatiles were stripped (rotary evaporator) and the remainder was taken up in dichloromethane (30 ml) and water (30 ml) and shaken in a separatory funnel. The organic phase was collected and the aqueous phase was back extracted with dichloromethane (2×25 ml). The organic extracts were combined, dried from magnesium sulfate, filtered and stripped. The crude was purified by silica gel chromatography (1 g, eluting with 7.5% methanol in dichloromethane) providing the desired product 1-[3-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-2-hydroxymethyl-phenyl]-3-[4-(1-hydroxy-1-methyl-ethyl)-phenylamino]-1H-pyrazole-4-carboxylic acid amide as an off-white powder (32 mg). LC/MS calcd for C32H33FN6O4 (m/e) 584.66, obsd 583 (M−H, ES−).

Workup

  1. custom(rotary evaporator)
  2. stirringwater (30 ml) and shaken in a separatory funnel
  3. customThe organic phase was collected
  4. extractionthe aqueous phase was back extracted with dichloromethane (2×25 ml)
  5. dry with materialdried from magnesium sulfate
  6. filtrationfiltered
  7. customThe crude was purified by silica gel chromatography (1 g, eluting with 7.5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-658fcce3552145519c7fd2ee32b31929
Source dataset
uspto-grants-2014_05
Patent number
US08729078B2

Reaction notes

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