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

HRID 1807749Notes

Reaction equation

HRID 1807749 reaction equation
[CH:1]1([CH2:4][NH:5][C:6](=[O:17])[NH:7][C:8]2[CH:16]=[CH:15][C:11]([C:12]([OH:14])=O)=[CH:10][CH:9]=2)[CH2:3][CH2:2]1.[N:18]1([CH2:25][C:26]2[CH:31]=[CH:30][C:29]([C:32]([OH:41])([C:37]([F:40])([F:39])[F:38])[C:33]([F:36])([F:35])[F:34])=[CH:28][CH:27]=2)[CH2:24][CH2:23][CH2:22][NH:21][CH2:20][CH2:19]1.C(N(CC)CC)C.Cl.CN(C)CCCN=C=NCC>ClCCl>[CH:1]1([CH2:4][NH:5][C:6]([NH:7][C:8]2[CH:9]=[CH:10][C:11]([C:12]([N:21]3[CH2:22][CH2:23][CH2:24][N:18]([CH2:25][C:26]4[CH:27]=[CH:28][C:29]([C:32]([OH:41])([C:37]([F:38])([F:39])[F:40])[C:33]([F:36])([F:34])[F:35])=[CH:30][CH:31]=4)[CH2:19][CH2:20]3)=[O:14])=[CH:15][CH:16]=2)=[O:17])[CH2:2][CH2:3]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 580558194-(3-(Cyclopropylmethyl)ureido)benzoic acidHCID 866385612-(4-((1,4-Diazepan-1-yl)methyl)phenyl)-1,1,1,3,3,3-hexafluoropropan-2-ol

Product 1

HCID 866385621-(Cyclopropylmethyl)-3-(4-(4-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)-1,4-diazepane-1-carbonyl)phenyl)ureaYield 63.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of 4-(3-(cyclopropylmethyl)ureido)benzoic acid (2.134 mmol, 0.5 g), 2-(4-((1,4-diazepan-1-yl)methyl)phenyl)-1,1,1,3,3,3-hexafluoropropan-2-ol (2.134 mmol, 0.761 g) and triethylamine (5.34 mmol, 0.744 mL, 0.540 g) in dichloromethane (30 mL) was added N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (2.56 mmol, 0.491 g). The reaction was stirred for 24 hours then was chromatographed on silica eluting with dichloromethane to dichloromethane/methanol (6%) then re-chromatographed on silica eluting with ethyl acetate to ethyl acetate/methanol (2%) to give the title compound (780 mg). MS (ESI) m/z 573.0 [M+H]+

Workup

  1. customthen was chromatographed on silica eluting with dichloromethane to dichloromethane/methanol (6%)
  2. customthen re-chromatographed on silica eluting with ethyl acetate to ethyl acetate/methanol (2%)

Sources & evidence

ORD record
ord-d0ec0242bd444ff59d839c77978c650c
Source dataset
uspto-grants-2013_01
Patent number
US08357679B2

Reaction notes

Loading…