3,5-Difluorobenzylamine → HCID 58986328, compound

HRID 420801Notes

Reaction equation

HRID 420801 reaction equation
[CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([O:17][CH2:18][O:19][CH3:20])=[CH:14][CH:15]=2)[C:10]([CH:21]=O)=[C:9]1[CH:23]([CH3:25])[CH3:24])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:26][C:27]1[CH:28]=[C:29]([CH:32]=[C:33]([F:35])[CH:34]=1)[CH2:30][NH2:31].C([BH3-])#N.[Na+]>CO.C(O)(=O)C>[CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([O:17][CH2:18][O:19][CH3:20])=[CH:14][CH:15]=2)[C:10]([CH2:21][NH:31][CH2:30][C:29]2[CH:28]=[C:27]([F:26])[CH:34]=[C:33]([F:35])[CH:32]=2)=[C:9]1[CH:23]([CH3:25])[CH3:24])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 1452113,5-Difluorobenzylamine2×HCID 5003444Sodium cyanoborohydrideHCID 58986320HCID 58986320, compound2×

Product 1

HCID 58986328HCID 58986328, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 887MethanolSolvent

Procedure

To a solution of 1-benzyl-2-isopropyl-5-(methoxymethoxy)-1H-indole-3-carboxaldehyde (Compound 4, 103 mg, 0.31 mmol) in methanol (5.0 ml) was added 3,5-difluorobenzylamine (49 μl, 0.40 mmol), and acetic acid (2 drops). After stirring at room temperature for 1 h, sodium cyanoborohydride (29 mg, 0.47 mmol) was added and the reaction was stirred for 5 h. More 3,5-difluorobenzylamine (50 μl, 0.40 mmol) was added, and the reaction was stirred for 64 h. The solvent was removed and the crude reaction mixture was purified by flash chromatography on silica gel eluting with 10-50% EtOAc-hexanes to yield 1-(1-benzyl-2-isopropyl-5-(methoxymethoxy)-1H-indol-3-yl)-N-(3,5-difluorobenzyl)methanamine (Compound 5) as a light greenish yellow oil.

Workup

  1. stirringthe reaction was stirred for 5 h
  2. stirringthe reaction was stirred for 64 h
  3. customThe solvent was removed
  4. customthe crude reaction mixture
  5. customwas purified by flash chromatography on silica gel eluting with 10-50% EtOAc-hexanes

Sources & evidence

ORD record
ord-7c89de3c358947cbbcd1e81e5fe489e1
Source dataset
uspto-grants-2012_01
Patent number
US08097644B2

Reaction notes

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