Hydrochloric Acid → HCID 178511543, compound

HRID 1819425Notes

Reaction equation

HRID 1819425 reaction equation
C(OC(=O)[NH:7][CH:8]1[CH2:13][CH2:12][CH:11]([CH2:14][NH:15][C:16]2[C:21]([F:22])=[CH:20][N:19]=[C:18](Cl)[N:17]=2)[CH2:10][CH2:9]1)(C)(C)C.Cl.[F:26][C:27]([F:38])([F:37])[O:28][C:29]1[CH:36]=[CH:35][CH:34]=[CH:33][C:30]=1[CH2:31][NH2:32]>CCOC(C)=O>[NH2:7][C@H:8]1[CH2:9][CH2:10][C@H:11]([CH2:14][NH:15][C:16]2[C:21]([F:22])=[CH:20][N:19]=[C:18]([NH:32][CH2:31][C:30]3[CH:33]=[CH:34][CH:35]=[CH:36][C:29]=3[O:28][C:27]([F:26])([F:37])[F:38])[N:17]=2)[CH2:12][CH2:13]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 2777251(2-(Trifluoromethoxy)phenyl)methanamineHCID 59845697{4-[(2-Chloro-5-fluoro-pyrimidin-4-ylamino)-methyl]-cyclohexyl}-carbamic acid tert-butyl ester

Product 1

HCID 178511543HCID 178511543, compoundYield 15%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
180 °C

Procedure

{4-[(2-Chloro-5-fluoro-pyrimidin-4-ylamino)-methyl]-cyclohexyl}-carbamic acid tert-butyl ester (127 mg, 0.35 mmol) was dissolved in 2-trifluoromethoxybenzylamine (2.5 mL) and heated at 180° C. for 20 min. The reaction mixture was diluted with EtOAc and poured into 1N HCl. The aqueous layer was separated and extracted with EtOAc (×2). The combined organic phase was dried over anhydrous Na2SO4 and concentrated in vacuo. The resulting residue was dissolved in CH2Cl2 (2.5 mL) and TFA (2.5 mL) was added. The reaction mixture was stirred at room temperature for 1 h. The reaction mixture was concentrated in vacuo and the resulting residue was diluted with EtOAc. The solution was poured into 10% NaHCO3 and the aqueous layer was re-extracted with EtOAc. The combined organic phase was dried over anhydrous Na2SO4 and concentrated in vacuo. The resulting residue was purified by silica gel preparative TLC using 9:1:0.1 CH2Cl2:MeOH:NH4OH as an eluent to afford 22 mg (15%) of the title compound, m/z 414.6 (M+1)+.

Workup

  1. customThe aqueous layer was separated
  2. extractionextracted with EtOAc (×2)
  3. dry with materialThe combined organic phase was dried over anhydrous Na2SO4
  4. concentrationconcentrated in vacuo
  5. dissolutionThe resulting residue was dissolved in CH2Cl2 (2.5 mL)
  6. additionTFA (2.5 mL) was added
  7. concentrationThe reaction mixture was concentrated in vacuo
  8. additionthe resulting residue was diluted with EtOAc
  9. additionThe solution was poured into 10% NaHCO3
  10. extractionthe aqueous layer was re-extracted with EtOAc
  11. dry with materialThe combined organic phase was dried over anhydrous Na2SO4
  12. concentrationconcentrated in vacuo
  13. customThe resulting residue was purified by silica gel preparative TLC

Sources & evidence

ORD record
ord-d46c8db25d8244d09b478ba7109e336c
Source dataset
uspto-grants-2009_10
Patent number
US07601714B2

Reaction notes

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