Trifluoroacetic acid → HCID 117653820, compound

HRID 530120Notes

Reaction equation

Cl[C:2]1[N:11]=[CH:10][C:9]2[N:8]([C:12]3[CH:13]=[C:14]([CH:17]=[CH:18][CH:19]=3)[C:15]#[N:16])[C:7](=[O:20])[C@@H:6]([CH3:21])[N:5]([CH:22]3[CH2:27][CH2:26][C:25]([F:29])([F:28])[CH2:24][CH2:23]3)[C:4]=2[N:3]=1.[F:30][C:31]1[CH:32]=[C:33]([NH2:40])[CH:34]=[C:35]2[C:39]=1[NH:38][N:37]=[CH:36]2.FC(F)(F)C(O)=O>C(O)C(F)(F)F.C(OCC)(=O)C>[F:29][C:25]1([F:28])[CH2:24][CH2:23][CH:22]([N:5]2[C:4]3[N:3]=[C:2]([NH:40][C:33]4[CH:34]=[C:35]5[C:39](=[C:31]([F:30])[CH:32]=4)[NH:38][N:37]=[CH:36]5)[N:11]=[CH:10][C:9]=3[N:8]([C:12]3[CH:13]=[C:14]([CH:17]=[CH:18][CH:19]=3)[C:15]#[N:16])[C:7](=[O:20])[C@H:6]2[CH3:21])[CH2:27][CH2:26]1

Participants

Conditions

Temperature: 125 °C

Procedure

To a solution of 3-[(7R)-2-chloro-8-(4,4-difluorocyclohexyl)-7-methyl-6-oxo-7,8-dihydropteridin-5(6H)-yl]benzonitrile (208 mg, 0.5 mmol), 7-fluoro-1H-indazol-5-amine (113 mg, 0.75 mmol) in trifluoroethanol (2 mL) in a microwave reaction vial was added trifluoroacetic acid (171 mg). The vial was then sealed and heated in a microwave reactor at 125° C. for 30 minutes. The reaction mixture was then diluted with ethyl acetate (25 mL) and washed with aqueous saturated aq. sodium bicarbonate. The organic layer was dried (Na2SO4) and evaporated to give a crude material, which was then purified by silica gel column chromatography (eluent: 2% methanol in dichloromethane) to give the desired product (40%).

Workup

customThe vial was then sealed
washwashed with aqueous saturated aq. sodium bicarbonate
dry with materialThe organic layer was dried (Na2SO4)
customevaporated
customto give a crude material, which
customwas then purified by silica gel column chromatography (eluent: 2% methanol in dichloromethane)

Sources & evidence

ORD record: ord-3056daf2ffc24f3aa43f9b8fcbb16b92
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09351974B2

Reaction notes

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