(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

HRID 216962Notes

Reaction equation

HRID 216962 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]1

Participants

3

Reactant 1

HCID 59568571(S)-tert-Butyl 4-(2-(4'-carbamoyl-3'-fluorobiphenyl-4-yl)-1-cyanoethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

Product 1

HCID 49783905(S)-4-Amino-N-(2-(4'-carbamoyl-3'-fluorobiphenyl-4-yl)-1-cyanoethyl)tetrahydro-2H-pyran-4-carboxamideYield 61%

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

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).

Workup

  1. customVolatiles were removed under reduced pressure
  2. customthe residue azeotroped with methanol
  3. customThe residue was purified by reversed phase
  4. washThe residue was converted to the free base by elution through a PL-HCO3 MP cartridge in dichloromethane/methanol

Sources & evidence

ORD record
ord-27a0e3f5f1b545b781a0b6f14c375ea7
Source dataset
uspto-grants-2012_06
Patent number
US08193239B2

Reaction notes

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