Triethylamine → 1-(Cyclopropylmethyl)-3-(2-fluoro-4-(4-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)-3-oxopiperazine-1-carbonyl)phenyl)urea

HRID 1807784Notes

Reaction equation

HRID 1807784 reaction equation
[NH2:1][C:2]1[CH:33]=[CH:32][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][C:15]3[CH:20]=[CH:19][C:18]([C:21]([OH:30])([C:26]([F:29])([F:28])[F:27])[C:22]([F:25])([F:24])[F:23])=[CH:17][CH:16]=3)[C:10](=[O:31])[CH2:9]2)=[O:7])=[CH:4][C:3]=1[F:34].[C:35](Cl)(=O)[O:36]C1C=CC([N+]([O-])=O)=CC=1.[CH:48]1([CH2:51][NH2:52])[CH2:50][CH2:49]1.C(N(CC)CC)C>O1CCOCC1.ClCCl>[CH:48]1([CH2:51][NH:52][C:35]([NH:1][C:2]2[CH:33]=[CH:32][C:5]([C:6]([N:8]3[CH2:13][CH2:12][N:11]([CH2:14][C:15]4[CH:16]=[CH:17][C:18]([C:21]([OH:30])([C:22]([F:23])([F:24])[F:25])[C:26]([F:28])([F:29])[F:27])=[CH:19][CH:20]=4)[C:10](=[O:31])[CH2:9]3)=[O:7])=[CH:4][C:3]=2[F:34])=[O:36])[CH2:50][CH2:49]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 75646CyclopropanemethanamineHCID 821294-Nitrophenyl chloroformateHCID 86638572HCID 86638572, compound

Product 1

HCID 591758461-(Cyclopropylmethyl)-3-(2-fluoro-4-(4-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)-3-oxopiperazine-1-carbonyl)phenyl)ureaYield 18.8%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of 4-(4-amino-3-fluorobenzoyl)-1-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)piperazin-2-one (0.405 mmol, 200 mg) and 4-nitrophenyl carbonochloridate (0.405 mmol, 82 mg) in 1,4-dioxane (2 mL) was stirred at room temperature for 30 minutes. Cyclopropylmethanamine (0.405 mmol, 28.8 mg) and triethylamine (1.216 mmol, 123 mg) were added and the reaction stirred at room temperature overnight. The reaction mixture was diluted with dichloromethane (10 mL) and washed with saturated aqueous sodium hydrogen carbonate solution (10 mL). The organic phase was concentrated and the resulting residue was purified by column chromatography on silica gel (eliciting with 3% methanol/97% dichloromethane—10% methanol/90% dichloromethane gradient) to afford the title compound (45 mg).

Workup

  1. washwashed with saturated aqueous sodium hydrogen carbonate solution (10 mL)
  2. concentrationThe organic phase was concentrated
  3. customthe resulting residue was purified by column chromatography on silica gel (eliciting with 3% methanol/97% dichloromethane—10% methanol/90% dichloromethane gradient)

Sources & evidence

ORD record
ord-24bce50c5c1c46188e18fce34c6b01fb
Source dataset
uspto-grants-2013_01
Patent number
US08357679B2

Reaction notes

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