Water → HCID 68295031, compound

HRID 1854120Notes

Reaction equation

HRID 1854120 reaction equation
[CH:1]1([N:6]2[C:14]3[CH:13]=[C:12]([C:15]4[CH:20]=[CH:19][CH:18]=[C:17](CO)[CH:16]=4)[CH:11]=[C:10]([C:23]([NH:25][CH2:26][C:27]4[C:28](=[O:35])[NH:29][C:30](C)=[CH:31][C:32]=4[CH3:33])=[O:24])[C:9]=3[CH:8]=[N:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[C:36]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:55]([Br:59])(Br)(Br)Br.O>C(Cl)Cl>[Br:59][CH2:55][C:17]1[CH:16]=[C:15]([C:12]2[CH:11]=[C:10]([C:23]([NH:25][CH2:26][C:27]3[C:28](=[O:35])[N:29]([CH3:36])[CH:30]=[CH:31][C:32]=3[CH3:33])=[O:24])[C:9]3[CH:8]=[N:7][N:6]([CH:1]4[CH2:5][CH2:4][CH2:3][CH2:2]4)[C:14]=3[CH:13]=2)[CH:20]=[CH:19][CH:18]=1

Participants

6

Reactant 4

HCID 962WaterHCID 11205Carbon tetrabromideHCID 11776TriphenylphosphineHCID 68294786HCID 68294786, compound

Product 1

HCID 68295031HCID 68295031, compoundYield 74.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 1-cyclopentyl-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridine-3-yl)methyl)-6-(3-(hydroxymethyl)phenyl)-1H-indazole-4-carboxamide (1.2 g, 2.6 mmol) in DCM (15 mL), triphenyl phosphine (2 g, 7.7 mmol) was added and reaction mixture stirred at room temperature for 10 min. Finally CBr4 (2.53 g, 7.65 mmol) was added portion-wise and resulting solution was stirred at room temperature for 18 h. On completion, water was added to the reaction mixture and aqueous layer extracted with 10% MeOH/DCM. Combined organic layer was dried over sodium sulfate and concentrated to give crude material which was purified by column chromatography over silica gel (60-120 mesh size) to afford 6-(3-(bromomethyl)phenyl)-1-cyclopentyl-N-((dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1H-indazole-4-carboxamide (1.0 g, 74.1%).

Workup

  1. customreaction mixture
  2. customresulting solution
  3. stirringwas stirred at room temperature for 18 h
  4. extractionextracted with 10% MeOH/DCM
  5. dry with materialCombined organic layer was dried over sodium sulfate
  6. concentrationconcentrated
  7. customto give crude material which
  8. customwas purified by column chromatography over silica gel (60-120 mesh size)

Sources & evidence

ORD record
ord-4b7d301424204dca90ca78165a6adf0c
Source dataset
uspto-grants-2015_02
Patent number
US08962620B2

Reaction notes

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