Phosphorus oxychloride → N-(2-Acetyl-5-methoxyphenyl)-2-((1-methylethyl)amino)-4-thiazolecarboxamide

HRID 2242448Notes

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]=[C:19]([O:21][CH3:22])[CH:18]=[CH:17][C:16]=1[C:23](=[O:25])[CH3:24].O=P(Cl)(Cl)Cl.C([O-])(O)=O.[Na+]>N1C=CC=CC=1>[C:23]([C:16]1[CH:17]=[CH:18][C:19]([O:21][CH3:22])=[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:25])[CH3:24]

Participants

Conditions

Temperature: -30 °C

Procedure

A mixture of compound 69 (4.4 g, 16.5 mmol) and the aniline derivative 66 (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 70 (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-b0877d65bb664233b6271bdec90e99b9
Source dataset: uspto-grants-2010_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07671032B2

Reaction notes

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