Triethylamine → 3-((4-(4-Amino-3-fluorobenzoyl)piperazin-1-y)methyl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)benzamide

HRID 1878421Notes

Reaction equation

HRID 1878421 reaction equation
[N:1]1([CH2:7][C:8]2[CH:9]=[C:10]([CH:21]=[CH:22][CH:23]=2)[C:11]([NH:13][C:14]([CH3:20])([CH3:19])[C:15]([F:18])([F:17])[F:16])=[O:12])[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[NH2:24][C:25]1[CH:33]=[CH:32][C:28]([C:29](O)=[O:30])=[CH:27][C:26]=1[F:34].C(N(CC)CC)C.CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O>ClCCl>[NH2:24][C:25]1[CH:33]=[CH:32][C:28]([C:29]([N:4]2[CH2:5][CH2:6][N:1]([CH2:7][C:8]3[CH:9]=[C:10]([CH:21]=[CH:22][CH:23]=3)[C:11]([NH:13][C:14]([CH3:20])([CH3:19])[C:15]([F:16])([F:18])[F:17])=[O:12])[CH2:2][CH2:3]2)=[O:30])=[CH:27][C:26]=1[F:34]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 99714-Amino-3-fluorobenzoic acidHCID 111923Propylphosphonic anhydrideHCID 668782073-(piperazin-1-ylmethyl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)benzamide

Product 1

HCID 579176513-((4-(4-Amino-3-fluorobenzoyl)piperazin-1-y)methyl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)benzamideYield 70.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

3-(Piperazin-1-ylmethyl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)benzamide (1.518 mmol, 0.5 g), 4-amino-3-fluorobenzoic acid (1.518 mmol, 0.235 g) and triethylamine (3.80 mmol, 0.529 mL, 0.384 g) were dissolved in dichloromethane (15.18 mL) and stirred for 5 minutes. 1-Propanephosphonic acid cyclic anhydride (3.04 mmol, 1,799 mL, 1.932 g, 50% solution in ethyl acetate) was added dropwise and the reaction mixture was allowed to stir for 1 hour. Dichloromethane was added and the organic mixture was washed with saturated sodium hydrogen carbonate, water, and saturated sodium chloride. The organic phase was dried with sodium sulfate, filtered and concentrated to yield the title compound (500 mg). MS (ESI) m/z 467.4 [M+H]+

Workup

  1. stirringto stir for 1 hour
  2. washthe organic mixture was washed with saturated sodium hydrogen carbonate, water, and saturated sodium chloride
  3. dry with materialThe organic phase was dried with sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-fb6f2506c09b4d949c007ec6145c3e25
Source dataset
uspto-grants-2012_11
Patent number
US08314091B2

Reaction notes

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