Acetonitrile → 3-(2-(2-aminopyrimidin-5-yl)ethynyl)-4-methyl-N-(3-(trifluoromethyl)phenyl)benzamide

HRID 1042632Notes

Reaction equation

HRID 1042632 reaction equation
[C:1]([C:3]1[CH:4]=[N:5][C:6]([NH2:9])=[N:7][CH:8]=1)#[CH:2].I[C:11]1[CH:12]=[C:13]([CH:27]=[CH:28][C:29]=1[CH3:30])[C:14]([NH:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([C:23]([F:26])([F:25])[F:24])[CH:18]=1)=[O:15].CC#N>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I.CCN(CC)CC>[NH2:9][C:6]1[N:7]=[CH:8][C:3]([C:1]#[C:2][C:28]2[CH:27]=[C:13]([CH:12]=[CH:11][C:29]=2[CH3:30])[C:14]([NH:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([C:23]([F:25])([F:26])[F:24])[CH:18]=2)=[O:15])=[CH:4][N:5]=1

Participants

7

Reactant 3

HCID 6342AcetonitrileHCID 161090215-Ethynylpyrimidin-2-amineHCID 171975693-iodo-4-methyl-N-(3-(trifluoromethyl)phenyl)benzamide

Product 1

HCID 115457023-(2-(2-aminopyrimidin-5-yl)ethynyl)-4-methyl-N-(3-(trifluoromethyl)phenyl)benzamide

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8471TriethylamineSolvent

Conditions

Temperature
90 °C

Procedure

To a sealable tube containing 5-ethynylpyrimidin-2-amine (172 mg, 1.44 mmol), PdCl2(PPh3)2 (25 mg, 0.036 mmol), 3-iodo-4-methyl-N-(3-(trifluoromethyl)phenyl)benzamide (292 mg, 0.72 mmol) was added MeCN (10 mL) and Et3N (3 mL) followed by CuI (6.8 mg, 0.036 mmol). The tube was sealed and heated at 90° C. for 1 h. The reaction was allowed to cool to room temperature and concentrated under reduced pressure. The resulting brown solid was reconstituted in MeOH:CH2Cl2 (1:1, 10 mL) and silica gel was added and reconcentrated. The silica-gel combined crude mixture was purified via automated flash chromatography (silica gel, 0 to 5% MeOH in CH2Cl2, gradient elution) to afford 3-(2-(2-aminopyrimidin-5-yl)ethynyl)-4-methyl-N-(3-(trifluoromethyl)phenyl)benzamide. MS m/z=397 [M+H]+. Calc'd for C21H15F3N4O: 396

Workup

  1. customThe tube was sealed
  2. temperatureto cool to room temperature
  3. concentrationconcentrated under reduced pressure
  4. additionsilica gel was added
  5. customwas purified
  6. washflash chromatography (silica gel, 0 to 5% MeOH in CH2Cl2, gradient elution)

Sources & evidence

ORD record
ord-793d88d9b4ce4229bdc8aecf36949bda
Source dataset
uspto-grants-2013_10
Patent number
US08557996B2

Reaction notes

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