Acetic Anhydride → N-[[2-[(2R,6S)-2,6-dimethyl-4-morpholinyl]-5-(2,6-dimethyl-4-pyridinyl)-4-thiazolyl]methyl]-acetamide

HRID 473982Notes

Reaction equation

HRID 473982 reaction equation
[CH3:1][C@H:2]1[O:7][C@@H:6]([CH3:8])[CH2:5][N:4]([C:9]2[S:10][C:11]([C:16]3[CH:21]=[C:20]([CH3:22])[N:19]=[C:18]([CH3:23])[CH:17]=3)=[C:12](NC)[N:13]=2)[CH2:3]1.[CH2:24]([N:26]([CH2:29]C)CC)[CH3:25].C(OC(=O)C)(=[O:33])C>ClCCl>[CH3:8][C@H:6]1[O:7][C@@H:2]([CH3:1])[CH2:3][N:4]([C:9]2[S:10][C:11]([C:16]3[CH:17]=[C:18]([CH3:23])[N:19]=[C:20]([CH3:22])[CH:21]=3)=[C:12]([CH2:29][NH:26][C:24](=[O:33])[CH3:25])[N:13]=2)[CH2:5]1

Participants

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 67216071[2-(cis-2,6-Dimethyl-morpholin-4-yl)-5-(2,6-dimethyl-pyridin-4-yl)-thiazol-4-yl]-methylamine

Product 1

HCID 53237123N-[[2-[(2R,6S)-2,6-dimethyl-4-morpholinyl]-5-(2,6-dimethyl-4-pyridinyl)-4-thiazolyl]methyl]-acetamideYield 59.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of Intermediate 5 (150 mg, 0.45 mmol) and triethylamine (0.063 mL, 0.54 mmol) was stirred in dichloromethane (6 mL) at room temperature. Acetic acid anhydride (0.051 mL, 0.54 mmol) was added and the reaction mixture was stirred at room temperature for 2 h. The reaction mixture was washed with a potassium carbonate solution. The organic layer was dried on MgSO4, filtered, and evaporated. The residue was purified by preparative HPLC (RP Shandon Hyperprep C18 BDS—8 μm, 250 g, 5 cm; mobile phase (0.25% NH4HCO3 solution in water, MeOH+CH3CN)), yielding 100 mg (59%) of Compound 60.

Workup

  1. washThe reaction mixture was washed with a potassium carbonate solution
  2. customThe organic layer was dried on MgSO4
  3. filtrationfiltered
  4. customevaporated
  5. customThe residue was purified by preparative HPLC (RP Shandon Hyperprep C18 BDS—8 μm, 250 g, 5 cm; mobile phase (0.25% NH4HCO3 solution in water, MeOH+CH3CN))

Sources & evidence

ORD record
ord-4435f6b8aee34d05a7423ccff5df4417
Source dataset
uspto-grants-2014_01
Patent number
US08637510B2

Reaction notes

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