Trifluoroacetic acid → N-(4-((2-aminopyridin-4-yl)oxy)-2,5-difluorophenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

HRID 476378Notes

Reaction equation

HRID 476378 reaction equation
[F:1][C:2]1[CH:22]=[C:21]([NH:23][C:24]([C:26]2([C:29](=[O:38])[NH:30][C:31]3[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=3)[CH2:28][CH2:27]2)=[O:25])[C:20]([F:39])=[CH:19][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]([NH:11]C(=O)OC(C)(C)C)[CH:6]=1.C(O)(C(F)(F)F)=O.C([O-])(O)=O.[Na+]>C(Cl)Cl>[NH2:11][C:7]1[CH:6]=[C:5]([O:4][C:3]2[C:2]([F:1])=[CH:22][C:21]([NH:23][C:24]([C:26]3([C:29]([NH:30][C:31]4[CH:32]=[CH:33][C:34]([F:37])=[CH:35][CH:36]=4)=[O:38])[CH2:28][CH2:27]3)=[O:25])=[C:20]([F:39])[CH:19]=2)[CH:10]=[CH:9][N:8]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 66604716Tert-butyl 4-(2,5-difluoro-4-(1-(4-fluorophenylcarbamoyl)cyclopropanecarboxamido)phenoxy)pyridin-2-ylcarbamate

Product 1

HCID 59596940N-(4-((2-aminopyridin-4-yl)oxy)-2,5-difluorophenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamideYield 82.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 4-(2,5-difluoro-4-(1-(4-fluorophenylcarbamoyl)cyclopropanecarboxamido)phenoxy)pyridin-2-ylcarbamate (1.8 g, 3.3 mmol) in CH2Cl2 (100 mL) was added TFA (5 mL) and the mixture was stirred at room temperature overnight. The reaction mixture was adjusted to pH>7 with saturated NaHCO3 solution and the separated organic layer was washed with brine, dried over Na2SO4 and concentrated under reduced pressure to give N-(4-((2-aminopyridin-4-yl)oxy)-2,5-difluorophenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (1.2 g, yield 82% yield). 1H-NMR (400 MHz, DMSO-d6): δ 10.99 (s, 1H), 9.76 (s, 1H), 8.04 (dd, J=12.4, 7.6 Hz, 1H), 7.79 (d, J=6.0 Hz, 1H), 7.58-7.55 (m, 2H), 7.47 (dd, J=10.8, 7.2 Hz, 1H), 7.16 (t, J=8.8 Hz, 2H), 6.16 (dd, J=6.0, 2.4 Hz, 1H), 6.00 (br s, 2H), 5.81 (d, J=2.0 Hz, 1H), 1.65-1.62 (m, 2H), 1.56-1.53 (m, 2H); MS (ESI): m/z 443.1 [M+H]+.

Workup

  1. washthe separated organic layer was washed with brine
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-8a618e636e8841eba8a6a6652d4e58e8
Source dataset
uspto-grants-2014_01
Patent number
US08637672B2

Reaction notes

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