Phosphorus oxychloride → 5-Chloro-7-(2,4-difluorophenyl)-2-[1-(propan-2-yl)piperidin-4-yl][1,2,4]triazolo[1,5-c]pyrimidine hydrochloride

HRID 2088686Notes

Reaction equation

P(Cl)(Cl)([Cl:3])=O.[F:6][C:7]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:8]=1[C:14]1[NH:19][C:18](=O)[N:17]2[N:21]=[C:22]([CH:24]3[CH2:29][CH2:28][N:27]([CH:30]([CH3:32])[CH3:31])[CH2:26][CH2:25]3)[N:23]=[C:16]2[CH:15]=1>[Cl-].C([N+](CC)(CC)CC)C1C=CC=CC=1>[ClH:3].[Cl:3][C:18]1[N:17]2[N:21]=[C:22]([CH:24]3[CH2:29][CH2:28][N:27]([CH:30]([CH3:32])[CH3:31])[CH2:26][CH2:25]3)[N:23]=[C:16]2[CH:15]=[C:14]([C:8]2[CH:9]=[CH:10][C:11]([F:13])=[CH:12][C:7]=2[F:6])[N:19]=1

Participants

Conditions

Temperature: 120 °C

Procedure

4.5 ml of phosphoryl chloride were added to 670 mg (1.72 mmol) of 7-(2,4-difluorophenyl)-2-[1-(propan-2-yl)piperidin-4-yl][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one (Example 51A), 785 mg (3.45 mmol) of benzyltriethylammonium chloride were added and the reaction mixture was stirred at 120° C. for 7 h. The reaction mixture was concentrated and carefully, with vigorous stirring, added to ice. Three times, the aqueous phase was extracted with dichloromethane. The combined organic phases were freed from the solvent and used without further purification. This gave 590 mg (80% of theory) of the product.

Workup

additionwere added
concentrationThe reaction mixture was concentrated
additioncarefully, with vigorous stirring, added to ice
extractionThree times, the aqueous phase was extracted with dichloromethane
customused without further purification

Sources & evidence

ORD record: ord-66d6830e2db04b5fb7eabc29df13352f
Source dataset: uspto-grants-2013_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08436003B2

Reaction notes

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