Trifluoroacetic acid → N-(2-((6-(3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methylureido)pyrimidin-4-yl)amino)-5-(piperazin-1-yl)phenyl)acrylamide

HRID 58205Notes

Reaction equation

HRID 58205 reaction equation
[C:1]([NH:5][C:6]1[CH:7]=[C:8]([N:51]2[CH2:56][CH2:55][N:54](C(OC(C)(C)C)=O)[CH2:53][CH2:52]2)[CH:9]=[CH:10][C:11]=1[N:12](C(OC(C)(C)C)=O)[C:13]1[CH:18]=[C:17]([N:19]([CH3:43])[C:20]([N:22]([C:31]2[C:36]([Cl:37])=[C:35]([O:38][CH3:39])[CH:34]=[C:33]([O:40][CH3:41])[C:32]=2[Cl:42])COCC[Si](C)(C)C)=[O:21])[N:16]=[CH:15][N:14]=1)(=[O:4])[CH:2]=[CH2:3].C(O)(C(F)(F)F)=O.[NH4+].[OH-]>C(Cl)Cl>[Cl:37][C:36]1[C:35]([O:38][CH3:39])=[CH:34][C:33]([O:40][CH3:41])=[C:32]([Cl:42])[C:31]=1[NH:22][C:20](=[O:21])[N:19]([C:17]1[N:16]=[CH:15][N:14]=[C:13]([NH:12][C:11]2[CH:10]=[CH:9][C:8]([N:51]3[CH2:52][CH2:53][NH:54][CH2:55][CH2:56]3)=[CH:7][C:6]=2[NH:5][C:1](=[O:4])[CH:2]=[CH2:3])[CH:18]=1)[CH3:43]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 14923Ammonium HydroxideHCID 131736987HCID 131736987, compound

Product 1

HCID 118025964N-(2-((6-(3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methylureido)pyrimidin-4-yl)amino)-5-(piperazin-1-yl)phenyl)acrylamideYield 94.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

tert-butyl 4-(3-acrylamido-4-((tert-butoxycarbonyl)(6-(3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methyl-3-((2-(trimethylsilyl)ethoxy)methyl)ureido)pyrimidin-4-yl)amino)phenyl)piperazine-1-carboxylate (59 g, 0.06 mmol) was stirred in DCM (2.0 ml). TFA (97 μl, 1.3 mmol) was added and the mixture was stirred at room temperature for 6 hours. The reaction mixture was evaporated. The remaining residue was dissolved in DCM and washed with saturated NaHCO3, dried over MgSO4 and evaporated. The resulting material was dissolved in THF (2.0 ml) and NH4OH (74 μl, 1.9 mmol) was added. The reaction mixture was stirred at room temperature for 5 minutes. The reaction mixture was evaporated to obtain the title compound (34 mg, yield: 90%) which was taken to the next step without further purification. 1H-NMR (400 MHz, DMSO-d) δ 2.62 (br. s., 4H) 3.08-3.27 (m, 7H) 3.77-4.03 (m, 6H) 5.72 (d, 1H) 6.11-6.34 (m, 2H) 6.40-6.62 (m, 1H) 6.70-6.98 (m, 2H) 7.22-7.37 (m, 2H) 8.32 (s, 1H) 8.70 (s, 1H) 9.58 (br. s., 1H) 12.06 (s, 1H); ESI-MS: 601 [M+H]+.

Workup

  1. customThe reaction mixture was evaporated
  2. dissolutionThe remaining residue was dissolved in DCM
  3. washwashed with saturated NaHCO3
  4. dry with materialdried over MgSO4
  5. customevaporated
  6. dissolutionThe resulting material was dissolved in THF (2.0 ml)
  7. stirringThe reaction mixture was stirred at room temperature for 5 minutes
  8. customThe reaction mixture was evaporated

Sources & evidence

ORD record
ord-2befc5d1073041cb9ce92f229076431d
Source dataset
uspto-grants-2016_09
Patent number
US09434697B2

Reaction notes

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