Triethylamine → 3-((4-(4-Amino-3-fluorobenzoyl)piperazin-1-yl)methyl)-N-(3,3-difluorocyclobutyl)benzamide

HRID 1878435Notes

Reaction equation

HRID 1878435 reaction equation
[F:1][C:2]1([F:22])[CH2:5][CH:4]([NH:6][C:7](=[O:21])[C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([CH2:14][N:15]3[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]3)[CH:9]=2)[CH2:3]1.[NH2:23][C:24]1[CH:32]=[CH:31][C:27]([C:28](O)=[O:29])=[CH:26][C:25]=1[F:33].C(N(CC)CC)C.CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O>ClCCl>[NH2:23][C:24]1[CH:32]=[CH:31][C:27]([C:28]([N:18]2[CH2:17][CH2:16][N:15]([CH2:14][C:10]3[CH:9]=[C:8]([CH:13]=[CH:12][CH:11]=3)[C:7]([NH:6][CH:4]3[CH2:5][C:2]([F:1])([F:22])[CH2:3]3)=[O:21])[CH2:20][CH2:19]2)=[O:29])=[CH:26][C:25]=1[F:33]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 99714-Amino-3-fluorobenzoic acidHCID 111923Propylphosphonic anhydrideHCID 57917681N-(3,3-difluorocyclobutyl)-3-(piperazin-1-ylmethyl)benzamide

Product 1

HCID 579176123-((4-(4-Amino-3-fluorobenzoyl)piperazin-1-yl)methyl)-N-(3,3-difluorocyclobutyl)benzamideYield 54.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

N-(3,3-Difluorocyclobutyl)-3-(piperazin-1-ylmethyl)benzamide (5.14 mmol, 1.59 g), 4-amino-3-fluorobenzoic acid (5.14 mmol, 0.797 g) and triethylamine (15.42 mmol, 2.143 mL, 1.560 g) were stirred in dichloromethane (30 mL) at room temperature. 1-Propanephosphonic acid cyclic anhydride (7.71 mmol, 4.59 mL, 4.91 g, 50% solution in ethyl acetate) was added dropwise and the reaction stirred for 1 hour. The reaction mixture was concentrated under vacuum and the residue taken up in ethyl acetate. The organic phase was washed with saturated sodium hydrogen carbonate solution, dried over sodium sulfate and concentrated under vacuum to afford the title compound (1.255 g). MS (ESI) m/z 447.5 [M+H]+

Workup

  1. concentrationThe reaction mixture was concentrated under vacuum
  2. washThe organic phase was washed with saturated sodium hydrogen carbonate solution
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-20a053c343bf4fd59361af7d4bac0e14
Source dataset
uspto-grants-2012_11
Patent number
US08314091B2

Reaction notes

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