Sodium borohydride → HCID 71008484, compound

HRID 1025594Notes

Reaction equation

HRID 1025594 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:35]=[O:36])=[C:19]([N:23]3[C:31]4[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=4)[C:25]([C:32]([NH2:34])=[O:33])=[CH: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.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]([CH2:35][OH:36])=[C:19]([N:23]3[C:31]4[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=4)[C:25]([C:32]([NH2:34])=[O:33])=[CH: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 86673711HCID 86673711, compound

Product 1

HCID 71008484HCID 71008484, compoundYield 69.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

To a cooled (ice bath) flask containing 1-(3-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-2-formylphenyl)-1H-indole-3-carboxamide (51 mg, 0.11 mmol) dissolved in methanol/dichloromethane (1.35 ml, 2.9:1) was added a solution of sodium borohydride (20 mg, 0.53 mmol) in water (0.35 ml), via slow drop-wise addition. The mixture was stirred for 10 minutes and then taken up in dichloromethane (20 ml) and water (20 ml). The contents were poured into a separatory funnel and agitated. The organic phase was collected and washed with a solution of 50% diluted brine (20 ml). The dichloromethane layer was collected and the aqueous phases were back extracted with methylene chloride (2×20 mL). The organic phases were combined, dried over magnesium sulfate, filtered and stripped. The crude material was purified by filtration through a short column of silica gel, eluting with 7.5% methanol/dichloromethane. The desired fraction was collected and then the material was crystallized from a solution of hot dichloromethane/hexanes to provide white crystalline product as 1-(3-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-2-(hydroxymethyl)phenyl)-1H-indole-3-carboxamide (37 mg). LC/MS calcd for C28H25FN4O3 (m/e) 484.54, obsd 485.0 (M+H, ES+): 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.44 (s, 9H) 4.03-4.37 (m, 2H) 5.49-6.00 (br. s, 2H) 7.18-7.38 (m, 3H) 7.49-7.71 (m, 5H) 8.13-8.28 (m, 2H) 8.32 (d, J=2.64 Hz, 1H).

Workup

  1. temperatureTo a cooled (ice bath) flask
  2. additionvia slow drop-wise addition
  3. additionThe contents were poured into a separatory funnel
  4. stirringagitated
  5. customThe organic phase was collected
  6. washwashed with a solution of 50% diluted brine (20 ml)
  7. customThe dichloromethane layer was collected
  8. extractionthe aqueous phases were back extracted with methylene chloride (2×20 mL)
  9. dry with materialdried over magnesium sulfate
  10. filtrationfiltered
  11. filtrationThe crude material was purified by filtration through a short column of silica gel
  12. washeluting with 7.5% methanol/dichloromethane
  13. customThe desired fraction was collected
  14. customthe material was crystallized from a solution of hot dichloromethane/hexanes

Sources & evidence

ORD record
ord-51d9edf5205b4186a24cf557490270ed
Source dataset
uspto-grants-2014_05
Patent number
US08729078B2

Reaction notes

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