Cyclopropanemethanamine → 3-((4-(4-(3-(Cyclopropylmethyl)ureido)-3-fluorobenzoyl)piperazin-1-yl)methyl)-N-(3,3-difluorocyclobutyl)benzamide

HRID 1878436Notes

Reaction equation

HRID 1878436 reaction equation
[NH2:1][C:2]1[CH:31]=[CH:30][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][C:15]3[CH:16]=[C:17]([CH:27]=[CH:28][CH:29]=3)[C:18]([NH:20][CH:21]3[CH2:24][C:23]([F:26])([F:25])[CH2:22]3)=[O:19])[CH2:10][CH2:9]2)=[O:7])=[CH:4][C:3]=1[F:32].C(N(C(C)C)C(C)C)C.[C:42](=[O:53])(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl.[CH:54]1([CH2:57][NH2:58])[CH2:56][CH2:55]1>ClCCl>[CH:54]1([CH2:57][NH:58][C:42](=[O:53])[NH:1][C:2]2[CH:31]=[CH:30][C:5]([C:6]([N:8]3[CH2:13][CH2:12][N:11]([CH2:14][C:15]4[CH:16]=[C:17]([CH:27]=[CH:28][CH:29]=4)[C:18]([NH:20][CH:21]4[CH2:22][C:23]([F:26])([F:25])[CH2:24]4)=[O:19])[CH2:10][CH2:9]3)=[O:7])=[CH:4][C:3]=2[F:32])[CH2:56][CH2:55]1

Participants

6

Reactant 4

HCID 75646CyclopropanemethanamineHCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 579176123-((4-(4-Amino-3-fluorobenzoyl)piperazin-1-yl)methyl)-N-(3,3-difluorocyclobutyl)benzamide

Product 1

HCID 579176633-((4-(4-(3-(Cyclopropylmethyl)ureido)-3-fluorobenzoyl)piperazin-1-yl)methyl)-N-(3,3-difluorocyclobutyl)benzamideYield 62.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 3-((4-(4-amino-3-fluorobenzoyl)piperazin-1-yl)methyl)-N-(3,3-difluorocyclobutyl)benzamide (0.224 mmol, 0.1 g) and N-ethyl-N-isopropylpropan-2-amine (0.672 mmol, 0.111 mL, 0.087 g) in dichloromethane were added dropwise to a stirred solution of bis(trichloromethyl) carbonate (0.083 mmol, 0.025 g) in dichloromethane (10 mL). The reaction mixture was allowed to stir for 30 minutes at room temperature. Cyclopropylmethylamine (0.448 mmol, 0.039 mL, 0.032 g) was added and the reaction mixture allowed to stir for a further 2 hours. The reaction mixture was washed with water and the organic phase was concentrated under vacuum. The resulting residue was purified by acidic reverse phase HPLC and converted to the free base to afford the title compound (28 mg). MS (ESI) m/z 544.5 [M+H]+

Workup

  1. stirringto stir for a further 2 hours
  2. washThe reaction mixture was washed with water
  3. concentrationthe organic phase was concentrated under vacuum
  4. customThe resulting residue was purified by acidic reverse phase HPLC

Sources & evidence

ORD record
ord-02e1dbd2803a4a3a8d8b1ae9c1ee951e
Source dataset
uspto-grants-2012_11
Patent number
US08314091B2

Reaction notes

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