Methyl N-(triethylammoniosulfonyl)carbamate → (S)-4-Amino-N-(1-cyano-2-(4-(2-methoxypyridin-4-yl)phenyl)ethyl)tetrahydro-2H-pyran-4-carboxamide

HRID 216964Notes

Reaction equation

HRID 216964 reaction equation
[NH2:1][C:2](=O)[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][N:14]=[C:13]([O:17][CH3:18])[CH:12]=2)=[CH:7][CH:6]=1.CC[N+](S(N=C(OC)[O-])(=O)=O)(CC)CC>ClCCl.C(O)=O>[NH2:28][C:22]1([C:20]([NH:19][C@H:3]([C:2]#[N:1])[CH2:4][C:5]2[CH:6]=[CH:7][C:8]([C:11]3[CH:16]=[CH:15][N:14]=[C:13]([O:17][CH3:18])[CH:12]=3)=[CH:9][CH:10]=2)=[O:21])[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1

Participants

5

Reactant 2

HCID 2724994Methyl N-(triethylammoniosulfonyl)carbamateHCID 59568572(S)-tert-Butyl 4-(1-amino-3-(4-(2-methoxypyridin-4-yl)phenyl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

Product 1

HCID 49783906(S)-4-Amino-N-(1-cyano-2-(4-(2-methoxypyridin-4-yl)phenyl)ethyl)tetrahydro-2H-pyran-4-carboxamideYield 58.2%

Reagents, catalysts & solvents 2

HCID 284Formic AcidSolventHCID 6344DichloromethaneSolvent

Procedure

(S)-tert-Butyl 4-(1-amino-3-(4-(2-methoxypyridin-4-yl)phenyl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (Example 26, step (i), 214 mg) in dichloromethane (10 mL) was treated with Burgess' reagent (205 mg) and the mixture was stirred at room temperature for 18 h. The solvent was evaporated to give a residue that was dissolved in formic acid (2 mL) which was heated at 50° C. for 15 min. The mixture was evaporated and then methanol was added and the solvent was evaporated. The product was purified by reversed phase HPLC using methanol in 0.1% aqueous TFA 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 (95 mg).

Workup

  1. customThe solvent was evaporated
  2. customto give a residue that
  3. temperaturewas heated at 50° C. for 15 min
  4. customThe mixture was evaporated
  5. additionmethanol was added
  6. customthe solvent was evaporated
  7. customThe product was purified by reversed phase
  8. washThe residue was converted to the free base by elution through a PL-HCO3 MP cartridge in dichloromethane/methanol

Sources & evidence

ORD record
ord-4d0b585ba0e146bb8f93bb28d35fe8f0
Source dataset
uspto-grants-2012_06
Patent number
US08193239B2

Reaction notes

Loading…