(S)-tert-Butyl 4-(2-(4'-carbamoyl-3'-fluorobiphenyl-4-yl)-1-cyanoethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate → (S)-4-Amino-N-(2-(4'-carbamoyl-3'-fluorobiphenyl-4-yl)-1-cyanoethyl)tetrahydro-2H-pyran-4-carboxamide
Reaction equation
[C:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:15]=[CH:14][C:13]([CH2:16][C@H:17]([NH:20][C:21]([C:23]3([NH:29]C(=O)OC(C)(C)C)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]3)=[O:22])[C:18]#[N:19])=[CH:12][CH:11]=2)=[CH:6][C:5]=1[F:37])(=[O:3])[NH2:2]>C(O)=O>[NH2:29][C:23]1([C:21]([NH:20][C@H:17]([C:18]#[N:19])[CH2:16][C:13]2[CH:12]=[CH:11][C:10]([C:7]3[CH:8]=[CH:9][C:4]([C:1](=[O:3])[NH2:2])=[C:5]([F:37])[CH:6]=3)=[CH:15][CH:14]=2)=[O:22])[CH2:24][CH2:25][O:26][CH2:27][CH2:28]1Participants
3
Reactant 1
Product 1
Reagents, catalysts & solvents 1
Procedure
(S)-tert-Butyl 4-(2-(4′-carbamoyl-3′-fluorobiphenyl-4-yl)-1-cyanoethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (Example 25, step (i), 108 mg) in formic acid (2 mL) was heated at 50° C. for 20 mins. Volatiles were removed under reduced pressure and the residue azeotroped with methanol. The residue was purified by reversed phase HPLC using methanol in 0.1% aqueous TFA solution as eluent. The residue was converted to the free base by elution through a PL-HCO3 MP cartridge in dichloromethane/methanol to afford the titled compound (53 mg).