Pyridine → Methyl 4-{[(4'-chloro-4-methylbiphenyl-3-yl)acetyl]amino}-1,3-thiazole-5-carboxylate

HRID 625667Notes

Reaction equation

HRID 625667 reaction equation
[NH2:1][C:2]1[N:3]=[CH:4][S:5][C:6]=1[C:7]([O:9][CH3:10])=[O:8].N1C=CC=CC=1.[Cl:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]2[CH:29]=[CH:28][C:27]([CH3:30])=[C:26]([CH2:31][C:32](Cl)=[O:33])[CH:25]=2)=[CH:20][CH:19]=1>C(#N)C>[Cl:17][C:18]1[CH:19]=[CH:20][C:21]([C:24]2[CH:29]=[CH:28][C:27]([CH3:30])=[C:26]([CH2:31][C:32]([NH:1][C:2]3[N:3]=[CH:4][S:5][C:6]=3[C:7]([O:9][CH3:10])=[O:8])=[O:33])[CH:25]=2)=[CH:22][CH:23]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 15832487Methyl 4-amino-1,3-thiazole-5-carboxylateHCID 23390525(4'-Chloro-4-methylbiphenyl-3-yl)acetyl chloride

Product 1

HCID 89825919Methyl 4-{[(4'-chloro-4-methylbiphenyl-3-yl)acetyl]amino}-1,3-thiazole-5-carboxylateYield 39.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

1.8 g (11.38 mmol) of methyl 4-amino-1,3-thiazole-5-carboxylate were dissolved in 40 acetonitrile, and 1.8 ml (22.76 mmol) of pyridine were added. After 5 min of stirring at room temperature (RT), a solution of 3.18 g (11.38 mmol) of (4′-chloro-4-methylbiphenyl-3-yl)acetyl chloride (obtained from (4′-chloro-4-methylbiphenyl-3-yl)acetic acid according to WO 99/48869 A1) in 20 ml of acetonitrile was added dropwise. The mixture was stirred at RT for 12 h. The precipitate formed was filtered off, washed with water and dried under reduced pressure. The resulting mother liquor was concentrated by evaporation, dissolved in chloroform and chromatographed (ethyl acetate/n-heptane: 20/80 to 80/20). This gives a total of 1.81 g of methyl 4-{[(4′-chloro-4-methylbiphenyl-3-yl)acetyl]amino}-1,3-thiazole-5-carboxylate.

Workup

  1. additionwere added
  2. stirringThe mixture was stirred at RT for 12 h
  3. customThe precipitate formed
  4. filtrationwas filtered off
  5. washwashed with water
  6. customdried under reduced pressure
  7. concentrationThe resulting mother liquor was concentrated by evaporation
  8. dissolutiondissolved in chloroform
  9. customchromatographed (ethyl acetate/n-heptane: 20/80 to 80/20)

Sources & evidence

ORD record
ord-c3f1ded5b6c44b689150b469866de505
Source dataset
uspto-grants-2016_04
Patent number
US09307767B2

Reaction notes

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