Acetic Anhydride → Acetic acid (S)-1-[5-(2-chloro-6-methyl-pyridin-4-yl)-3-(3-methoxy-5-trifluoromethyl-phenylamino)-[1,2,4]triazol-1-ylmethyl]-propyl ester

HRID 2092220Notes

Reaction equation

HRID 2092220 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([C:8]2[N:12]([CH2:13][C@@H:14]([OH:17])[CH2:15][CH3:16])[N:11]=[C:10]([NH:18][C:19]3[CH:24]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:22]=[C:21]([O:29][CH3:30])[CH:20]=3)[N:9]=2)[CH:5]=[C:4]([CH3:31])[N:3]=1.[C:32](OC(=O)C)(=[O:34])[CH3:33]>CN(C)C1C=CN=CC=1>[Cl:1][C:2]1[CH:7]=[C:6]([C:8]2[N:12]([CH2:13][C@@H:14]([O:17][C:32](=[O:34])[CH3:33])[CH2:15][CH3:16])[N:11]=[C:10]([NH:18][C:19]3[CH:24]=[C:23]([C:25]([F:27])([F:28])[F:26])[CH:22]=[C:21]([O:29][CH3:30])[CH:20]=3)[N:9]=2)[CH:5]=[C:4]([CH3:31])[N:3]=1

Participants

4

Reactant 2

HCID 7918Acetic AnhydrideHCID 86644738(S)-1-[5-(2-Chloro-6-methyl-pyridin-4-yl)-3-(3-methoxy-5-trifluoromethyl-phenylamino)-[1,2,4]triazol-1-yl]butan-2-ol

Product 1

HCID 86644739Acetic acid (S)-1-[5-(2-chloro-6-methyl-pyridin-4-yl)-3-(3-methoxy-5-trifluoromethyl-phenylamino)-[1,2,4]triazol-1-ylmethyl]-propyl ester

Reagents, catalysts & solvents 1

HCID 142844-(Dimethylamino)pyridineCatalyst

Procedure

N,N-Dimethyl-4-pyridinamine (0.1222 g, 0.001 mol) was added to a solution of intermediate D7 (9.117 g, 0.020 mol) in acetyl acetate (378 ml). The reaction mixture was stirred at reflux for 30 minutes. Subsequently, the mixture was cooled to room temperature and the solvent was evaporated in vacuo. The residue was redissolved in CH2Cl2. This organic solution was washed with a saturated sodium bicarbonate solution, washed with brine, and was subsequently dried (MgSO4), filtered and the solvent was evaporated in vacuo. The obtained yellow oil was purified by reversed-phase high-performance liquid chromatography (Shandon Hyperprep® C18 BDS (Base Deactivated Silica) 8 μm, 250 g, I.D. 5 cm). A gradient with 3 mobile phases was applied. Phase A: a 0.25% NH4HCO3 solution in water; phase B: methanol; phase C: CH3CN). The desired fractions were collected. The solvent was evaporated and co-evaporated with methanol. The product was crystallized from DIPE/heptane. The white crystals were filtered off and dried in vacuo. Yield: 3.677 g of intermediate D8 (37%; 5-enantiomer).

Workup

  1. temperatureat reflux for 30 minutes
  2. customthe solvent was evaporated in vacuo
  3. dissolutionThe residue was redissolved in CH2Cl2
  4. washThis organic solution was washed with a saturated sodium bicarbonate solution
  5. washwashed with brine
  6. dry with materialwas subsequently dried (MgSO4)
  7. filtrationfiltered
  8. customthe solvent was evaporated in vacuo
  9. customThe obtained yellow oil was purified by reversed-phase high-performance liquid chromatography (Shandon Hyperprep® C18 BDS (Base Deactivated Silica) 8 μm, 250 g, I.D. 5 cm)
  10. customThe desired fractions were collected
  11. customThe solvent was evaporated
  12. customThe product was crystallized from DIPE/heptane
  13. filtrationThe white crystals were filtered off
  14. customdried in vacuo

Sources & evidence

ORD record
ord-48a7f244182e432b90c1e3ad8d2737eb
Source dataset
uspto-grants-2013_05
Patent number
US08440701B2

Reaction notes

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