Trifluoroacetic acid → 4-(2-(4-Cyanophenylamino)-5-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-yloxy)-3,5-dimethylbenzonitrile

HRID 1805875Notes

Reaction equation

Cl[C:2]1[N:3]=[C:4]([O:12][C:13]2[C:20]([CH3:21])=[CH:19][C:16]([C:17]#[N:18])=[CH:15][C:14]=2[CH3:22])[C:5]2[N:10]([CH3:11])[CH:9]=[CH:8][C:6]=2[N:7]=1.[NH2:23][C:24]1[CH:31]=[CH:30][C:27]([C:28]#[N:29])=[CH:26][CH:25]=1.C(O)(C(F)(F)F)=O>O>[C:28]([C:27]1[CH:30]=[CH:31][C:24]([NH:23][C:2]2[N:3]=[C:4]([O:12][C:13]3[C:20]([CH3:21])=[CH:19][C:16]([C:17]#[N:18])=[CH:15][C:14]=3[CH3:22])[C:5]3[N:10]([CH3:11])[CH:9]=[CH:8][C:6]=3[N:7]=2)=[CH:25][CH:26]=1)#[N:29]

Participants

Conditions

Temperature: 90 °C

Procedure

In a sealed tube was added 4-(2-chloro-5-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-yloxy)-3,5-dimethylbenzonitrile (294 mg, 0.94 mmol), 4-aminobenzonitrile (455 mg, 3.77 mmol), TFE (3.1 mL) and TFA (0.58 mL, 7.52 mmol). The reaction mixture was stirred at 90° C. for 48 h. Upon completion of the reaction, the resulting mixture was cooled, diluted with water and washed with EtOAc. The combined organic layers were washed with NaHCO3, brine, dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by preparative TLC, eluting with hexanes:ethyl acetate (4:1-1:2), to give the product as an off-white solid (133 mg, 40%).

Workup

customUpon completion of the reaction
temperaturethe resulting mixture was cooled
washwashed with EtOAc
washThe combined organic layers were washed with NaHCO3, brine
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo
customThe crude product was purified by preparative TLC
washeluting with hexanes:ethyl acetate (4:1-1:2)

Sources & evidence

ORD record: ord-e7b70c48b69c4b7da9cd46d143ee50a9
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08354532B2

Reaction notes

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