Triethylamine → 1-(Cyclopropylmethyl)-3-(4-(4-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzoyl)piperazine-1-carbonyl)phenyl)urea

HRID 1807792Notes

Reaction equation

HRID 1807792 reaction equation
[CH:1]1([CH2:4][NH:5][C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]([N:17]3[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]3)=[O:16])=[CH:11][CH:10]=2)=[O:7])[CH2:3][CH2:2]1.[F:23][C:24]([F:41])([F:40])[C:25]([C:31]1[CH:39]=[CH:38][C:34]([C:35](O)=[O:36])=[CH:33][CH:32]=1)([OH:30])[C:26]([F:29])([F:28])[F:27].C(N(CC)CC)C.CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O>ClCCl.C(OCC)(=O)C.C(=O)([O-])[O-].[Na+].[Na+]>[CH:1]1([CH2:4][NH:5][C:6]([NH:8][C:9]2[CH:10]=[CH:11][C:12]([C:15]([N:17]3[CH2:22][CH2:21][N:20]([C:35](=[O:36])[C:34]4[CH:33]=[CH:32][C:31]([C:25]([OH:30])([C:24]([F:23])([F:40])[F:41])[C:26]([F:27])([F:28])[F:29])=[CH:39][CH:38]=4)[CH2:19][CH2:18]3)=[O:16])=[CH:13][CH:14]=2)=[O:7])[CH2:2][CH2:3]1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 111923Propylphosphonic anhydrideHCID 5911694-(1,1,1,3,3,3-Hexafluoro-2-hydroxypropan-2-yl)benzoic acidHCID 580558061-(Cyclopropylmethyl)-3-(4-(Piperazine-1-carbonyl)phenyl)urea

Product 1

HCID 591759121-(Cyclopropylmethyl)-3-(4-(4-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzoyl)piperazine-1-carbonyl)phenyl)ureaYield 19%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolventHCID 10340Sodium CarbonateSolvent

Procedure

To a solution of 1-(cyclopropylmethyl)-3-(4-(piperazine-1-carbonyl)phenyl)urea (1.654 mmol, 500 mg), 4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzoic acid (1.654 mmol, 476 mg) and triethylamine (4.96 mmol, 0.691 mL, 502 mg) in dichloromethane (50 mL) was added 1-propanephosphonic acid cyclic anhydride (2.480 mmol, 0.738 mL, 789 mg; 50% solution in ethyl acetate). The reaction mixture was stirred for 2 hours then was diluted with ethyl acetate and sodium carbonate (aqueous). The organic layer was separated, dried (magnesium carbonate) and concentrated under reduced pressure. The residue was chromatographed on silica eluting with a gradient of dichloromethane to ethyl acetate to give the title compound (180 mg). MS (ESI) m/z 571.0 [M−H]−

Workup

  1. customThe organic layer was separated
  2. dry with materialdried (magnesium carbonate)
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was chromatographed on silica eluting with a gradient of dichloromethane to ethyl acetate

Sources & evidence

ORD record
ord-91917fcbf6cf4835877f12379dafb4c2
Source dataset
uspto-grants-2013_01
Patent number
US08357679B2

Reaction notes

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