(S)-tert-Butyl 4-(1-cyano-2-(4-(4-methyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazin-7-yl)phenyl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate → (S)-4-Amino-N-(1-cyano-2-(4-(4-methyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazin-7-yl)phenyl)ethyl)tetrahydro-2H-pyran-4-carboxamide

HRID 216969Notes

Reaction equation

HRID 216969 reaction equation
[C:1]([C@@H:3]([NH:23][C:24]([C:26]1([NH:32]C(=O)OC(C)(C)C)[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1)=[O:25])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:12]=[CH:13][C:14]3[N:19]([CH3:20])[C:18](=[O:21])[CH2:17][S:16][C:15]=3[CH:22]=2)=[CH:7][CH:6]=1)#[N:2]>C(O)=O>[NH2:32][C:26]1([C:24]([NH:23][C@H:3]([C:1]#[N:2])[CH2:4][C:5]2[CH:6]=[CH:7][C:8]([C:11]3[CH:12]=[CH:13][C:14]4[N:19]([CH3:20])[C:18](=[O:21])[CH2:17][S:16][C:15]=4[CH:22]=3)=[CH:9][CH:10]=2)=[O:25])[CH2:27][CH2:28][O:29][CH2:30][CH2:31]1

Participants

3

Reactant 1

HCID 59568616(S)-tert-Butyl 4-(1-cyano-2-(4-(4-methyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazin-7-yl)phenyl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

Product 1

HCID 49783983(S)-4-Amino-N-(1-cyano-2-(4-(4-methyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazin-7-yl)phenyl)ethyl)tetrahydro-2H-pyran-4-carboxamideYield 51.9%

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Procedure

(S)-tert-Butyl 4-(1-cyano-2-(4-(4-methyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazin-7-yl)phenyl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (Example 28, step (iii), 120 mg) in formic acid (2 mL) was heated at 50° C. for 20 mins. The solvent was removed under reduced pressure and the residue azeotroped with methanol. The product was purified by reversed phase HPLC using methanol in 0.1% aqueous TFA and then converted to the free base by elution through a PL-HCO3 MP cartridge with dichloromethane/methanol to afford the titled compound (51 mg).

Workup

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

Sources & evidence

ORD record
ord-32fcbf83e1bb42dc9900db78ea6d2254
Source dataset
uspto-grants-2012_06
Patent number
US08193239B2

Reaction notes

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