Diisopropylamine → HCID 69058155, compound

HRID 1819466Notes

Reaction equation

HRID 1819466 reaction equation
[C:1]([O:5][C:6](=[O:36])[NH:7][C@H:8]1[CH2:13][CH2:12][C@H:11]([CH2:14][NH:15][C:16]2[C:21](Br)=[CH:20][N:19]=[C:18]([NH:23][CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[O:31][C:32]([F:35])([F:34])[F:33])[N:17]=2)[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].O1CCOCC1.C(NC(C)C)(C)C.[C:50]1([C:56]#[CH:57])[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1>[Cu]I.C1C=CC(C#N)=CC=1.C1C=CC(C#N)=CC=1.Cl[Pd]Cl.CCOC(C)=O>[C:1]([O:5][C:6](=[O:36])[NH:7][CH:8]1[CH2:13][CH2:12][CH:11]([CH2:14][NH:15][C:16]2[C:21]([C:57]#[C:56][C:50]3[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=3)=[CH:20][N:19]=[C:18]([NH:23][CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[O:31][C:32]([F:35])([F:34])[F:33])[N:17]=2)[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 7912DiisopropylamineHCID 10821PhenylacetyleneHCID 312751,4-DioxaneHCID 178453941HCID 178453941, compound

Product 1

HCID 69058155HCID 69058155, compound

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 498840Bis(benzonitrile)palladium chlorideCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

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. filtrationfiltered through a plug of SiO2
  2. concentrationThe filtrate was concentrated
  3. custompurified via flash chromatography (SiO2, 25% EtOAc-Hexanes)

Sources & evidence

ORD record
ord-b714aa0f4daa4b8f9158e553900ec211
Source dataset
uspto-grants-2009_10
Patent number
US07601714B2

Reaction notes

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