Isopropylamine → 1-(2-Fluoro-4-(4-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)piperazine-1-carbonyl)phenyl)-3-isopropylurea

HRID 1807722Notes

Reaction equation

HRID 1807722 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([N:10]2[CH2:15][CH2:14][N:13]([CH2:16][C:17]3[CH:22]=[CH:21][C:20]([C:23]([OH:32])([C:28]([F:31])([F:30])[F:29])[C:24]([F:27])([F:26])[F:25])=[CH:19][CH:18]=3)[CH2:12][CH2:11]2)=[O:9])=[CH:4][C:3]=1[F:33].[CH:34]([N:37]([CH2:41]C)C(C)C)([CH3:36])[CH3:35].ClC(Cl)([O:46]C(=O)OC(Cl)(Cl)Cl)Cl.C(N)(C)C>ClCCl>[F:33][C:3]1[CH:4]=[C:5]([C:8]([N:10]2[CH2:11][CH2:12][N:13]([CH2:16][C:17]3[CH:22]=[CH:21][C:20]([C:23]([OH:32])([C:24]([F:25])([F:26])[F:27])[C:28]([F:30])([F:31])[F:29])=[CH:19][CH:18]=3)[CH2:14][CH2:15]2)=[O:9])[CH:6]=[CH:7][C:2]=1[NH:1][C:41]([NH:37][CH:34]([CH3:36])[CH3:35])=[O:46]

Participants

6

Reactant 4

HCID 6363IsopropylamineHCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 86638550(4-Amino-3-fluorophenyl)(4-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)piperazin-1-yl)methanone

Product 1

HCID 591758511-(2-Fluoro-4-(4-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)piperazine-1-carbonyl)phenyl)-3-isopropylureaYield 46%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(4-Amino-3-fluorophenyl)(4-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-benzyl)piperazin-1-yl)methanone (0.209 mmol, 0.1 g) and N,N-diisopropylethylamine (0.709 mmol, 0.117 mL, 0.092 g) were stirred in dichloromethane at room temperature. Triphosgene (0.077 mmol, 0.023 g) was added and the reaction mixture stirred for 30 minutes. Isopropylamine (0.417 mmol, 0.036 mL, 0.025 g) was added and the reaction stirred for a further 30 minutes. The reaction was concentrated at reduced pressure and the resulting residue was purified by silica chromatography (eluting with a solvent gradient from dichloromethane to 5% methanol/dichloromethane) to afford the title compound (20 mg). MS (ESI) m/z 565.5 [M+H]+

Workup

  1. stirringthe reaction stirred for a further 30 minutes
  2. concentrationThe reaction was concentrated at reduced pressure
  3. customthe resulting residue was purified by silica chromatography (
  4. washeluting with a solvent gradient from dichloromethane to 5% methanol/dichloromethane)

Sources & evidence

ORD record
ord-8870325c031e4316a15a281cdc2cbc95
Source dataset
uspto-grants-2013_01
Patent number
US08357679B2

Reaction notes

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