Ammonia → (S)-4-Amino-N-(1-cyano-2-(3'-cyanobiphenyl-4-yl)ethyl)tetrahydro-2H-pyran-4-carboxamide

HRID 216924Notes

Reaction equation

[C:1]([C@@H:3]([NH:19][C:20]([C:22]1([NH:28]C(=O)OC(C)(C)C)[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1)=[O:21])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17]#[N:18])[CH:12]=2)=[CH:7][CH:6]=1)#[N:2].O.N>C(O)=O>[NH2:28][C:22]1([C:20]([NH:19][C@H:3]([C:1]#[N:2])[CH2:4][C:5]2[CH:6]=[CH:7][C:8]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([C:17]#[N:18])[CH:12]=3)=[CH:9][CH:10]=2)=[O:21])[CH2:23][CH2:24][O:25][CH2:26][CH2:27]1

Participants

Conditions

Temperature: 36 °C

Procedure

(S)-tert-butyl 4-(1-cyano-2-(3′-cyanobiphenyl-4-yl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (Example 8, step (ii), 282 mg) in formic acid (1.5 mL) was stirred at room temperature for 5 h, warmed at 36° C. for 30 mins then stirred at room temperature overnight. Water was added and the cooled solution was made basic with 0.880 ammonia and then extracted (×3) with dichloromethane. The combined organic extracts were dried over magnesium sulphate, filtered and the solvent was evaporated to yield an oil which was purified by chromatography on silica using 80% ethyl acetate in isohexane as eluent and then crystallised from isopropanol to yield a solid. The solid was washed with diethyl ether and dried to afford the titled compound (89 mg).

Workup

extractionextracted (×3) with dichloromethane
dry with materialThe combined organic extracts were dried over magnesium sulphate
filtrationfiltered
customthe solvent was evaporated
customto yield an oil which
customwas purified by chromatography on silica using 80% ethyl acetate in isohexane as eluent
customcrystallised from isopropanol
customto yield a solid
washThe solid was washed with diethyl ether
customdried

Sources & evidence

ORD record: ord-9641d5bc9e7345cbb8b7009d1582c899
Source dataset: uspto-grants-2012_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08193239B2

Reaction notes

Loading…