Thiazole → 2-[4-(Pyrid-3-yloxymethyl)-2-phenylbenzoyl]4-ethylthiazole-5-carboxylic acid ethyl ester

HRID 2121197Notes

Reaction equation

HRID 2121197 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:9][C:8](N)=[N:7][C:6]=1[CH2:11][CH3:12])=[O:4].C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[N:23]1[CH:28]=[CH:27][CH:26]=[C:25]([O:29][CH2:30][C:31]2[CH:39]=[CH:38][C:34]([C:35](O)=[O:36])=[C:33]([C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)[CH:32]=2)[CH:24]=1.[C:46](N1C=CN=C1)(N1C=CN=C1)=O.[N-]1C=CN=C1.S1C=CN=C1>CN(C=O)C.C1COCC1>[CH2:1]([O:2][C:3]([C:5]1[S:9][C:8]([C:35](=[O:36])[C:34]2[CH:38]=[CH:39][C:31]([CH2:30][O:29][C:25]3[CH:24]=[N:23][CH:28]=[CH:27][CH:26]=3)=[CH:32][C:33]=2[C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)=[N:7][C:6]=1[CH2:11][CH3:12])=[O:4])[CH3:46]

Participants

9

Reactant 6

HCID 9256ThiazoleHCID 682631,1'-CarbonyldiimidazoleHCID 735005Methyl 2-amino-4-ethyl-1,3-thiazole-5-carboxylateHCID 2733832Lithium HexamethyldisilazideHCID 3386966ImidazolateHCID 234363704-(3-Pyridyloxymethyl)2-phenylbenzoic acid

Product 1

HCID 536463072-[4-(Pyrid-3-yloxymethyl)-2-phenylbenzoyl]4-ethylthiazole-5-carboxylic acid ethyl esterYield 48.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a −12° C. solution in DMF (2 mL) of 2-amino-4-ethylthiazole-5-carboxylic acid methyl ester (80 mg, 0.40 mmol), prepared as described in J. Chem. Soc. Perkin 1, 1982, 154, was added lithium hexamethyldisilazide (1.0 M in THF, 0.76 mL, 0.76 mmol) and the resulting yellow solution was stirred for 30 minutes. In a separate flask 4-(3-pyridyloxymethyl)-2-phenylbenzoic acid (101 mg, 0.33 mmol), prepared as in Example 228D and carbonyldiimidazole (60 mg, 0.37 mmol) were dissolved in THF and stirred for 1 hour. The resulting imidazolide solution was then added to the thiazole solution at −10° C. and the mixture was stirred for 30 minutes. The cold bath was then removed and stirring was continued for 30 minutes. The reaction mixture was quenched with saturated aqueous ammonium chloride and poured into water. The mixture was extracted twice with dichloromethane. The combine organic extracts were dried, filtered and concentrated. The solid residue was recrystallized from ethyl acetate-methanol to give 2-[4-(pyrid-3-yloxymethyl)-2-phenylbenzoyl]4-ethylthiazole-5-carboxylic acid ethyl ester (75 mg).

Workup

  1. stirringstirred for 1 hour
  2. stirringthe mixture was stirred for 30 minutes
  3. customThe cold bath was then removed
  4. stirringstirring
  5. waitwas continued for 30 minutes
  6. customThe reaction mixture was quenched with saturated aqueous ammonium chloride
  7. additionpoured into water
  8. extractionThe mixture was extracted twice with dichloromethane
  9. customThe combine organic extracts were dried
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe solid residue was recrystallized from ethyl acetate-methanol

Sources & evidence

ORD record
ord-87888cd3bf61469b95f5c0919b5eba80
Source dataset
uspto-grants-2004_02
Patent number
US06693123B2

Reaction notes

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