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

HRID 515265Notes

Reaction equation

HRID 515265 reaction equation
[NH2:1][C:2]1[CH:31]=[CH:30][C:5]([O:6][CH:7]2[CH2:12][CH2:11][N:10]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([C:20]([OH:29])([C:25]([F:28])([F:27])[F:26])[C:21]([F:24])([F:23])[F:22])=[CH:16][CH:15]=3)[CH2:9][CH2:8]2)=[CH:4][CH:3]=1.[C:32](Cl)(=O)[O:33]C1C=CC([N+]([O-])=O)=CC=1.[CH:45]1([CH2:48][NH2:49])[CH2:47][CH2:46]1.C(N(CC)CC)C>ClCCl.C(=O)(O)[O-].[Na+]>[CH:45]1([CH2:48][NH:49][C:32]([NH:1][C:2]2[CH:3]=[CH:4][C:5]([O:6][CH:7]3[CH2:12][CH2:11][N:10]([CH2:13][C:14]4[CH:15]=[CH:16][C:17]([C:20]([OH:29])([C:21]([F:22])([F:23])[F:24])[C:25]([F:28])([F:26])[F:27])=[CH:18][CH:19]=4)[CH2:9][CH2:8]3)=[CH:30][CH:31]=2)=[O:33])[CH2:47][CH2:46]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 75646CyclopropanemethanamineHCID 821294-Nitrophenyl chloroformateHCID 86670926HCID 86670926, compound

Product 1

HCID 866709271-(Cyclopropylmethyl)-3-(4-(1-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)piperidin-4-yloxy)phenyl)ureaYield 22.7%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 516892Sodium BicarbonateSolvent

Procedure

A solution of 2-(4-((4-(4-aminophenoxy)piperidin-1-yl)methyl)phenyl)-1,1,1,3,3,3-hexafluoropropan-2-ol (0.446 mmol, 200 mg) and 4-nitrophenyl carbonochloridate (0.446 mmol, 90 mg) in dichloromethane (1 mL) were stirred at room temperature for 30 minutes. Cyclopropylmethanamine (0.892 mmol, 0.091 mL, 63.4 mg) was added, followed by triethylamine (1.338 mmol, 0.187 mL, 135 mg) and the reaction stirred at room temperature overnight. The reaction mixture was diluted with dichloromethane and saturated sodium bicarbonate solution was added. The organic layer was separated and concentrated under vacuum. The residue was purified by silica column chromatography (eluent 2-8% methanol in dichloromethane) to give the title compound (55.3 mg). MS (ESI) m/z 546.2 [M+H]+

Workup

  1. additionwas added
  2. customThe organic layer was separated
  3. concentrationconcentrated under vacuum
  4. customThe residue was purified by silica column chromatography (eluent 2-8% methanol in dichloromethane)

Sources & evidence

ORD record
ord-e34084d671af4d3cbfdbc7992cfcd254
Source dataset
uspto-grants-2015_08
Patent number
US09108939B2

Reaction notes

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