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

HRID 515272Notes

Reaction equation

HRID 515272 reaction equation
[CH:1]1([CH2:4][NH:5][C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH:16]3[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]3)=[CH:11][CH:10]=2)=[O:7])[CH2:3][CH2:2]1.[F:22][C:23]([F:40])([F:39])[C:24]([C:30]1[CH:38]=[CH:37][C:33]([C:34](O)=[O:35])=[CH:32][CH:31]=1)([OH:29])[C:25]([F:28])([F:27])[F:26].C(N(CC)CC)C.CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O>ClCCl>[CH:1]1([CH2:4][NH:5][C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH:16]3[CH2:21][CH2:20][N:19]([C:34](=[O:35])[C:33]4[CH:32]=[CH:31][C:30]([C:24]([OH:29])([C:23]([F:22])([F:39])[F:40])[C:25]([F:26])([F:27])[F:28])=[CH:38][CH:37]=4)[CH2:18][CH2:17]3)=[CH:11][CH:10]=2)=[O:7])[CH2:2][CH2:3]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 111923Propylphosphonic anhydrideHCID 5911694-(1,1,1,3,3,3-Hexafluoro-2-hydroxypropan-2-yl)benzoic acidHCID 671941431-(Cyclopropylmethyl)-3-(4-(piperidin-4-yloxy)phenyl)urea

Product 1

HCID 866709311-(Cyclopropylmethyl)-3-(4-(1-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzoyl)piperidin-4-yloxy)phenyl)ureaYield 4.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1-(cyclopropylmethyl)-3-(4-(piperidin-4-yloxy)phenyl)urea (1.037 mmol, 300 mg), 4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzoic acid (1.037 mmol, 299 mg) and triethylamine (3.11 mmol, 0.432 mL, 315 mg) were combined and stirred at room temperature in dichloromethane (5 mL). 1-Propanephosphonic acid cyclic anhydride (1.555 mmol, 0.926 mL, 990 mg; 50% solution in ethyl acetate) was added and the reaction stirred at room temperature for 1 hour. The reaction mixture was washed with saturated sodium bicarbonate solution and the organic layer was separated, dried and concentrated under vacuum. The residue was dissolved in dichloromethane and purified by silica column chromatography (eluent 2-8% methanol in dichloromethane) to afford the title compound (24 mg). MS (ESI) m/z 560.2 [M+H]+

Workup

  1. washThe reaction mixture was washed with saturated sodium bicarbonate solution
  2. customthe organic layer was separated
  3. customdried
  4. concentrationconcentrated under vacuum
  5. dissolutionThe residue was dissolved in dichloromethane
  6. custompurified by silica column chromatography (eluent 2-8% methanol in dichloromethane)

Sources & evidence

ORD record
ord-0ded12cd041946dab3aa486ce8856361
Source dataset
uspto-grants-2015_08
Patent number
US09108939B2

Reaction notes

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