Pyridine → N-(2-Acetyl-5-methoxyphenyl)-2-((1-methylethyl)amino)-4-thiazolecarboxamide
Reaction equation
Br.[CH:2]([NH:5][C:6]1[S:7][CH:8]=[C:9]([C:11]([OH:13])=O)[N:10]=1)([CH3:4])[CH3:3].[NH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[O:21]=P(Cl)(Cl)Cl.[C:26]([O-:29])(O)=O.[Na+].N1[CH:36]=[CH:35]C=CC=1>>[C:35]([C:16]1[CH:17]=[CH:18][C:19]([O:29][CH3:26])=[CH:20][C:15]=1[NH:14][C:11]([C:9]1[N:10]=[C:6]([NH:5][CH:2]([CH3:3])[CH3:4])[S:7][CH:8]=1)=[O:13])(=[O:21])[CH3:36]Participants
Conditions
- Temperature
- -30 °C
Procedure
A mixture of compound 46 (4.4 g, 16.5 mmol) and the aniline derivative 93 (2.75 g, 16.5 mmol) in pyridine (140 mL) was cooled to −30° C. (upon cooling, the clear solution became partially a suspension). POCl3 (3.3 mL, 35 mmol) was added slowly over a 5 min period. The mixture was stirred at −30° C. for 1 h, and was then allowed to assume rt. After stirring at rt for 1.5 h the reaction mixture was poured over ice, and the pH was adjusted to about 9-10 using solid and saturated NaHCO3. The crude product was extracted into CH2Cl2 (3×) and the combined organic phases were dried (MgSO4) and evaporated. The crude dark-beige solid was purified by flash column chromatography (hexane/EtOAc 55:45) to give compound 47 (5.6 g, 76%) as a pale yellow solid.
Workup
- temperatureupon cooling
- customto assume rt
- stirringAfter stirring at rt for 1.5 h the reaction mixture
- additionwas poured over ice
- extractionThe crude product was extracted into CH2Cl2 (3×)
- dry with materialthe combined organic phases were dried (MgSO4)
- customevaporated
- customThe crude dark-beige solid was purified by flash column chromatography (hexane/EtOAc 55:45)
Sources & evidence
- ORD record
- ord-3bbab1d7a2bd4e8781161ec39ec9102e
- Source dataset
- uspto-grants-2009_10
- Patent number
- US07608590B2
Reaction notes
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