Triethylamine → 1-(4-(4-(4-(2-(tert-Butyldimethylsilyloxy)-1,1,1,3,3,3-hexafluoropropan-2-yl)benzyl)piperazine-1-carbonyl)-2-fluorophenyl)-3-(pyridin-2-yl)urea

HRID 1807753Notes

Reaction equation

HRID 1807753 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]([O:32][Si:33]([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:35])[CH3:34])([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:40].[C:41](Cl)(=O)[O:42]C1C=CC([N+]([O-])=O)=CC=1.[N:54]1[CH:59]=[CH:58][CH:57]=[CH:56][C:55]=1[NH2:60].C(N(CC)CC)C>ClCCl>[Si:33]([O:32][C:23]([C:20]1[CH:19]=[CH:18][C:17]([CH2:16][N:13]2[CH2:14][CH2:15][N:10]([C:8]([C:5]3[CH:6]=[CH:7][C:2]([NH:1][C:41]([NH:60][C:55]4[CH:56]=[CH:57][CH:58]=[CH:59][N:54]=4)=[O:42])=[C:3]([F:40])[CH:4]=3)=[O:9])[CH2:11][CH2:12]2)=[CH:22][CH:21]=1)([C:24]([F:25])([F:26])[F:27])[C:28]([F:31])([F:29])[F:30])([C:36]([CH3:37])([CH3:39])[CH3:38])([CH3:34])[CH3:35]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 104392-AminopyridineHCID 821294-Nitrophenyl chloroformateHCID 59175907(4-Amino-3-fluorophenyl)(4-(4-(2-(tert-butyldimethylsilyloxy)-1,1,1,3,3,3-hexafluoropropan-2-yl)benzyl)piperazin-1-yl)methanone

Product 1

HCID 591758371-(4-(4-(4-(2-(tert-Butyldimethylsilyloxy)-1,1,1,3,3,3-hexafluoropropan-2-yl)benzyl)piperazine-1-carbonyl)-2-fluorophenyl)-3-(pyridin-2-yl)ureaYield 28.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(4-Amino-3-fluorophenyl)(4-(4-(2-(tert-butyldimethylsilyloxy)-1,1,1,3,3,3-hexa-fluoropropan-2-yl)benzyl)piperazin-1-yl)methanone (200 mg, 0.337 mmol) and 4-nitro-phenyl carbonochloridate (0.337 mmol, 0.068 g) were combined and stirred at room temperature for 1 hour in dichloromethane (1 mL). Pyridin-2-amine (0.674 mmol, 0.063 g) and triethylamine (0.674 mmol, 0.094 mL, 0.068 g) were added and the reaction mixture heated using microwave irradiation to 120° C. for 10 minutes. The reaction mixture was purified by silica column chromatography (eluant dichloromethane/methanol 0% to 2%) to afford the title compound (69 mg). MS (ESI) m/z 714.2 [M+H]+

Workup

  1. temperaturethe reaction mixture heated
  2. custommicrowave irradiation to 120° C. for 10 minutes
  3. customThe reaction mixture was purified by silica column chromatography (eluant dichloromethane/methanol 0% to 2%)

Sources & evidence

ORD record
ord-811953e34dd5403c8650f82da9611e4c
Source dataset
uspto-grants-2013_01
Patent number
US08357679B2

Reaction notes

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