Diisopropylethylamine → N-(4-(4-(1,2,4-Thiadiazol-5-ylamino)-6-(3-cyclopropyl-3-fluoroazetidin-1-yl)pyrimidin-2-ylthio)phenyl)cyclopropanecarboxamide

HRID 390427Notes

Reaction equation

[S:1]1[C:5]([NH:6][C:7]2[CH:12]=[C:11](Cl)[N:10]=[C:9]([S:14][C:15]3[CH:20]=[CH:19][C:18]([NH:21][C:22]([CH:24]4[CH2:26][CH2:25]4)=[O:23])=[CH:17][CH:16]=3)[N:8]=2)=[N:4][CH:3]=[N:2]1.Cl.[CH:28]1([C:31]2([F:35])[CH2:34][NH:33][CH2:32]2)[CH2:30][CH2:29]1.CCN(C(C)C)C(C)C>O1CCOCC1>[S:1]1[C:5]([NH:6][C:7]2[CH:12]=[C:11]([N:33]3[CH2:34][C:31]([CH:28]4[CH2:30][CH2:29]4)([F:35])[CH2:32]3)[N:10]=[C:9]([S:14][C:15]3[CH:20]=[CH:19][C:18]([NH:21][C:22]([CH:24]4[CH2:26][CH2:25]4)=[O:23])=[CH:17][CH:16]=3)[N:8]=2)=[N:4][CH:3]=[N:2]1

Participants

Conditions

Temperature: 130 °C

Procedure

A mixture of crude N-(4-(4-(1,2,4-Thiadiazol-5-ylamino)-6-chloropyrimidin-2-ylthio)phenyl)cyclopropanecarboxamide (780 mg, 1.93 mmol), 3-cyclopropyl -3-fluoroazetidine hydrochloride (818 mg, 5.4 mmol), DiPEA (0.7 mL, 4.6 mmol) in 1,4-dioxane (20 mL) was heated in the microwave to 130° C. for 20 minutes. The mixture was concentrated and purified by preparative HPLC to yield 34 mg of N-(4-(4-(1,2,4-Thiadiazol-5-ylamino)-6-(3-cyclopropyl-3-fluoroazetidin-1-yl)pyrimidin-2-ylthio)phenyl)cyclopropanecarboxamide with a purity of 95+% (HPLC method A, Rf=8.573 minutes).

Workup

concentrationThe mixture was concentrated
custompurified by preparative HPLC

Sources & evidence

ORD record: ord-8d68d23c42804013ac8887cd1b79dcff
Source dataset: uspto-grants-2013_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08383633B2

Reaction notes

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