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

HRID 2088685Notes

Reaction equation

P(Cl)(Cl)([Cl:3])=O.[Cl: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[Cl:6])[N:19]=1

Participants

Conditions

Temperature: 120 °C

Procedure

4.5 ml of phosphoryl chloride were added to 1.25 g (3.2 mmol) of 7-(2-chloro-4-fluorophenyl)-2-[1-(propan-2-yl)piperidin-4-yl][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one (Example 50A), 1.46 g (6.41 mmol) of benzyltriethylammonium chloride were added and the reaction mixture was stirred at 120° C. for 16 h. The reaction mixture was concentrated and carefully, with vigorous stirring, added to ice. The mixture was stirred for another 10 min. Three times, the aqueous phase was extracted with dichloromethane. The combined organic phases were freed from the solvent and the residue was dried under high vacuum. This gave 715 mg (55% of theory) of the product.

Workup

additionwere added
concentrationThe reaction mixture was concentrated
additioncarefully, with vigorous stirring, added to ice
stirringThe mixture was stirred for another 10 min
extractionThree times, the aqueous phase was extracted with dichloromethane
customthe residue was dried under high vacuum

Sources & evidence

ORD record: ord-7129db5fb6a64c9f97221b78868e6fa1
Source dataset: uspto-grants-2013_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08436003B2

Reaction notes

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