2-Amino-2-thioxoethyl 2,2-dimethylpropanoate → 5-(2-Hydroxymethyl-5-methyl-thiazol-4-yl)-6-methyl-2-oxo-1-(3-trifluoromethyl-phenyl)-1,2-dihydro-pyridine-3-carboxylic acid 4-methanesulfonyl-benzylamide

HRID 559810Notes

Reaction equation

HRID 559810 reaction equation
Br[CH:2]([CH3:37])[C:3]([C:5]1[CH:6]=[C:7]([C:23]([NH:25][CH2:26][C:27]2[CH:32]=[CH:31][C:30]([S:33]([CH3:36])(=[O:35])=[O:34])=[CH:29][CH:28]=2)=[O:24])[C:8](=[O:22])[N:9]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=2)[C:10]=1[CH3:11])=O.C([O:44][CH2:45][C:46]([NH2:48])=[S:47])(=O)C(C)(C)C>CCO>[CH3:36][S:33]([C:30]1[CH:31]=[CH:32][C:27]([CH2:26][NH:25][C:23]([C:7]2[C:8](=[O:22])[N:9]([C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:20])([F:19])[F:21])[CH:13]=3)[C:10]([CH3:11])=[C:5]([C:3]3[N:48]=[C:46]([CH2:45][OH:44])[S:47][C:2]=3[CH3:37])[CH:6]=2)=[O:24])=[CH:28][CH:29]=1)(=[O:35])=[O:34]

Participants

4

Reactant 2

HCID 27821132-Amino-2-thioxoethyl 2,2-dimethylpropanoateHCID 866147825-(2-bromopropanoyl)-6-methyl-N-[4-(methylsulfonyl)benzyl]-2-oxo-1-(3-(trifluoromethyl)phenyl)-1,2-dihydropyridine-3-carboxamide

Product 1

HCID 667254055-(2-Hydroxymethyl-5-methyl-thiazol-4-yl)-6-methyl-2-oxo-1-(3-trifluoromethyl-phenyl)-1,2-dihydro-pyridine-3-carboxylic acid 4-methanesulfonyl-benzylamideYield 68%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

5-(2-Bromopropanoyl)-6-methyl-N-[4-(methylsulfonyl)benzyl]-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2-dihydropyridine-3-carboxamide (Example 53 (b), 0.06 g, 0.10 mmol), 2-amino-2-thioxoethyl pivalate (0.022 g, 0.125 mmol), EtOH (2 ml) and a magnetic stirrer bar were placed in a tube designed for microwave synthesis. The vial was sealed and the mixture was heated in a CEM Discover Microwave apparatus (100 W, 80 ° C.) for 40 minutes, giving complete conversion of the starting material to a single product according to LC-MS. The solvents were evaporated to give a crude mixture which was purified on silica giving 0.045 g (76%) of the intermediate pivalyl ester. This compound was dissolved in THF (2 ml) and water (2 ml). To this solution was added NaOH (0.2 mmol, 0.1 ml of a 2M solution), and the mixture was stirred at room temperature overnight. The THF was evaporated off and the water phase was acidified, extracted, and lo the extracts were evaporated. Purification by preparative HPLC gave pure fractions which were freeze-dried to give the title compound (0.040 g, 68%) as a white solid.

Workup

  1. customdesigned for microwave synthesis
  2. customThe vial was sealed
  3. customgiving complete conversion of the starting material to a single product
  4. customThe solvents were evaporated
  5. customto give a crude mixture which
  6. customwas purified on silica giving 0.045 g (76%) of the intermediate pivalyl ester
  7. dissolutionThis compound was dissolved in THF (2 ml)
  8. additionTo this solution was added NaOH (0.2 mmol, 0.1 ml of a 2M solution), and the mixture
  9. customThe THF was evaporated off
  10. extractionextracted
  11. customwere evaporated
  12. customPurification by preparative HPLC
  13. customgave pure fractions which
  14. customwere freeze-dried

Sources & evidence

ORD record
ord-e4e44774e28b427392508cbdf81ed92a
Source dataset
uspto-grants-2011_11
Patent number
US08063073B2

Reaction notes

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