Trifluoroacetic acid → 4-(4-(4-Acetyl-2,6-dimethylphenoxy)-5-benzyl-5H-pyrrolo[3,2-d]pyrimidin-2-ylamino)benzonitrile

HRID 1805877Notes

Reaction equation

[CH2:1]([N:8]1[C:16]2[C:15]([O:17][C:18]3[C:23]([CH3:24])=[CH:22][C:21]([C:25](=[O:27])[CH3:26])=[CH:20][C:19]=3[CH3:28])=[N:14][C:13](Cl)=[N:12][C:11]=2[CH:10]=[CH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:30][C:31]1[CH:38]=[CH:37][C:34]([C:35]#[N:36])=[CH:33][CH:32]=1.C(O)(C(F)(F)F)=O>O>[C:25]([C:21]1[CH:22]=[C:23]([CH3:24])[C:18]([O:17][C:15]2[C:16]3[N:8]([CH2:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)[CH:9]=[CH:10][C:11]=3[N:12]=[C:13]([NH:30][C:31]3[CH:38]=[CH:37][C:34]([C:35]#[N:36])=[CH:33][CH:32]=3)[N:14]=2)=[C:19]([CH3:28])[CH:20]=1)(=[O:27])[CH3:26]

Participants

Conditions

Temperature: 90 °C

Procedure

In a sealed tube was added 1-(4-(5-benzyl-2-chloro-5H-pyrrolo[3,2-d]pyrimidin-4-yloxy)-3,5-dimethylphenyl)ethanone (111 mg, 0.27 mmol), 4-aminobenzonitrile (129 mg, 1.1 mmol), TFE (1.7 mL) and TFA (0.2 mL, 2.16 mmol). The reaction mixture was stirred at 90° C. for 16 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 and brine; dried over Na2SO4; filtered; and concentrated in vacuo. The crude product was purified by silica gel column chromatography, eluting with hexanes:ethyl acetate (9:1-100% EtOAc), to give the product as an off-white solid (68 mg, 51%).

Workup

customUpon completion of the reaction
temperaturethe resulting mixture was cooled
washwashed with EtOAc
washThe combined organic layers were washed with NaHCO3 and brine
dry with materialdried over Na2SO4
filtrationfiltered
concentrationand concentrated in vacuo
customThe crude product was purified by silica gel column chromatography
washeluting with hexanes

Sources & evidence

ORD record: ord-d661d6cb305d4c2ea70533cfdc1d47c2
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08354532B2

Reaction notes

Loading…