Tricyclohexylphosphine → 3-(2-(2-(cyclopropylamino)pyrimidin-5-yl)ethynyl)-4-methyl-N-(3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl)benzamide

HRID 80603Notes

Reaction equation

HRID 80603 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH:25]=[CH:26][C:27]=1[CH3:28])[C:6]([NH:8][C:9]1[CH:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[C:11]([N:19]2[CH:23]=[C:22]([CH3:24])[N:21]=[CH:20]2)[CH:10]=1)=[O:7])#[CH:2].Br[C:30]1[CH:31]=[N:32][C:33]([NH:36][CH:37]2[CH2:39][CH2:38]2)=[N:34][CH:35]=1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.CCN(C(C)C)C(C)C>[Cu]I.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH:37]1([NH:36][C:33]2[N:34]=[CH:35][C:30]([C:2]#[C:1][C:3]3[CH:4]=[C:5]([CH:25]=[CH:26][C:27]=3[CH3:28])[C:6]([NH:8][C:9]3[CH:14]=[C:13]([C:15]([F:16])([F:17])[F:18])[CH:12]=[C:11]([N:19]4[CH:23]=[C:22]([CH3:24])[N:21]=[CH:20]4)[CH:10]=3)=[O:7])=[CH:31][N:32]=2)[CH2:39][CH2:38]1

Participants

7

Reactant 4

HCID 75806TricyclohexylphosphineHCID 81531DiisopropylethylamineHCID 50233275-bromo-N-cyclopropylpyrimidin-2-amineHCID 866911383-ethynyl-4-methyl-N-(3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl)benzamide

Product 1

HCID 510374083-(2-(2-(cyclopropylamino)pyrimidin-5-yl)ethynyl)-4-methyl-N-(3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl)benzamide

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
60 °C

Procedure

In a pressure tube with one end sealed, add 192 mg step 3 product, 3-ethynyl-4-methyl-N-(3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl)benzamide (0.5 mmol), 107 mg Step 4 product, 5-bromo-N-cyclopropylpyrimidin-2-amine (0.5 mmol), 19 mg CuI (0.1 mmol), 2.2 mg Pd(OAc)2 (0.01 mmol), 2.8 mg PCy3 (0.01 mmol) 3.0 mL DMF, 193 mg DIPEA (1.5 mmol), after nitrogen replacement, the solution is heated to 60° C. for 12 h. After cooling to room temperature, the solid is filtered off by 2 cm silical gel column and washed by ethyl acetate for three times, and the solution was concentrated by vacuum evaporation for 193 mg desired product (75%).

Workup

  1. customIn a pressure tube with one end sealed
  2. temperatureAfter cooling to room temperature
  3. filtrationthe solid is filtered off by 2 cm silical gel column
  4. washwashed by ethyl acetate for three times
  5. concentrationthe solution was concentrated by vacuum evaporation for 193 mg desired product (75%)

Sources & evidence

ORD record
ord-ed4dda5d518b4c6c9f771abe2d26fcae
Source dataset
uspto-grants-2014_09
Patent number
US08846671B2

Reaction notes

Loading…