Trifluoroacetic acid → HCID 178511540, compound

HRID 1819467Notes

Reaction equation

HRID 1819467 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]([C:22]#[C:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[CH:20][N:19]=[C:18]([NH:30][CH2:31][C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=3[O:38][C:39]([F:42])([F:41])[F:40])[N:17]=2)[CH2:10][CH2:9]1)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:7][C@H:8]1[CH2:13][CH2:12][C@H:11]([CH2:14][NH:15][C:16]2[C:21]([C:22]#[C:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[CH:20][N:19]=[C:18]([NH:30][CH2:31][C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=3[O:38][C:39]([F:41])([F:42])[F:40])[N:17]=2)[CH2:10][CH2:9]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 69058155HCID 69058155, compound

Product 1

HCID 178511540HCID 178511540, compoundYield 57%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(trans-4-{[5-Bromo-2-(2-trifluoromethoxy-benzylamino)-pyrimidin-4-ylamino]-methyl}-cyclohexyl)-carbamic acid tert-butyl ester (100 mg, 0.174 mmol), CuI (0.97 mg, 0.005 mmol), and Pd(PhCN)2Cl2 (1.96 mg, 0.005 mmol) were dissolved in degassed dioxane (0.5 mmol). To this solution was added tri-(tert)-butylphosphine tetrafluoroborate (2.4 mg, 0.010 mmol) followed by diisopropylamine (0.029 mL, 0.2 mmol) and phenylacetylene (0.022 mL, 0.2 mmol). The reaction was stirred at 25° C. for 18 h. The reaction was worked up by the addition of EtOAc and filtered through a plug of SiO2. The filtrate was concentrated and purified via flash chromatography (SiO2, 25% EtOAc-Hexanes) to yield (4-{[5-phenylethynyl-2-(2-trifluoromethoxy-benzylamino)-pyrimidin-4-ylamino]-methyl}-cyclohexyl)-carbamic acid tert-butyl ester. (4-{[5-Phenylethynyl-2-(2-trifluoromethoxy-benzylamino)-pyrimidin-4-ylamino]-methyl}-cyclohexyl)-carbamic acid tert-butyl ester was dissolved in CH2Cl2 (0.5 mL) and TFA (0.5 mL) was added. The solution was stirred for 2 h and the volatiles were removed and the crude residue was purified via preparative thin layer chromatography (SiO2, 2000 micron thickness, 1:9:90 NH4OH:CH3OH:CH2Cl2) to afford 49 mg (57%) of N4-[(trans-4-aminocyclohexyl)methyl]-5-(phenylethynyl)-N2-[2-(trifluoromethoxy)benzyl]pyrimidine-2,4-diamine, m/z 496.58 [M+1]+.

Workup

  1. customthe volatiles were removed
  2. customthe crude residue was purified via preparative thin layer chromatography (SiO2, 2000 micron thickness, 1:9:90 NH4OH:CH3OH:CH2Cl2)

Sources & evidence

ORD record
ord-8b9668f1b1a943598c68a861357e57d0
Source dataset
uspto-grants-2009_10
Patent number
US07601714B2

Reaction notes

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