Diisopropylethylamine → N-(4-(4-(3-Cyclopropyl-3-fluoroazetidin-1-yl)-6-(pyridin-2-ylamino)pyrimidin-2-ylthio)phenyl)-3,3,3-trifluoropropanamide

HRID 390426Notes

Reaction equation

Cl[C:2]1[CH:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=2)[N:5]=[C:4]([S:15][C:16]2[CH:21]=[CH:20][C:19]([NH:22][C:23](=[O:29])[CH2:24][C:25]([F:28])([F:27])[F:26])=[CH:18][CH:17]=2)[N:3]=1.Cl.[CH:31]1([C:34]2([F:38])[CH2:37][NH:36][CH2:35]2)[CH2:33][CH2:32]1.CCN(C(C)C)C(C)C>O1CCOCC1>[CH:31]1([C:34]2([F:38])[CH2:37][N:36]([C:2]3[CH:7]=[C:6]([NH:8][C:9]4[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=4)[N:5]=[C:4]([S:15][C:16]4[CH:21]=[CH:20][C:19]([NH:22][C:23](=[O:29])[CH2:24][C:25]([F:28])([F:27])[F:26])=[CH:18][CH:17]=4)[N:3]=3)[CH2:35]2)[CH2:33][CH2:32]1

Participants

Conditions

Temperature: 140 °C

Procedure

N-(4-(4-chloro-6-(pyridin-2-ylamino)pyrimidin-2-ylthio)phenyl)-3,3,3-trifluoropropanamide (2b, 620 mg, 1.4 mmol) and 3-cyclopropyl-3-fluoroazetidine hydrochloride (598 mg, 3.94 mmol, 2.8 eq.) were dissolved in 1,4-dioxane and transferred to a microwave vial. DiPEA (437 mg, 3.38 mmol, 2.4 eq.) was added. The mixture was flushed with N2 for 10 minutes while stirring and heated at 140° C. for 30 minutes in the microwave. HPLC-MS analysis showed 27-40% product in the mixture. The mixture was concentrated and purified by preparative HPLC and lyophilized, yielding 28 mg (3.8%) of a light-yellow solid with a purity of 98+% (HPLC method B: Rf=5.855 minutes).

Workup

customThe mixture was flushed with N2 for 10 minutes
concentrationThe mixture was concentrated
custompurified by preparative HPLC

Sources & evidence

ORD record: ord-e0be0f8e0f2d4ae8b5b43f3dfb14d840
Source dataset: uspto-grants-2013_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08383633B2

Reaction notes

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