Cesium carbonate → 2-(1-(6-chloro-2-methylpyrimidin-4-yl)azetidin-3-yl)-1-methyl-1H-benzo[d]imidazole

HRID 2202818Notes

Reaction equation

[NH:1]1[CH2:4][CH:3]([C:5]2[N:9]([CH3:10])[C:8]3[CH:11]=[CH:12][CH:13]=[CH:14][C:7]=3[N:6]=2)[CH2:2]1.[Cl:15][C:16]1[CH:21]=[C:20](Cl)[N:19]=[C:18]([CH3:23])[N:17]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CC(N(C)C)=O.CCOC(C)=O>[Cl:15][C:16]1[N:17]=[C:18]([CH3:23])[N:19]=[C:20]([N:1]2[CH2:4][CH:3]([C:5]3[N:9]([CH3:10])[C:8]4[CH:11]=[CH:12][CH:13]=[CH:14][C:7]=4[N:6]=3)[CH2:2]2)[CH:21]=1

Participants

Conditions

Temperature: 50 °C

Procedure

Intermediate 1 (8.2 g, 43.8 mmol), 4,6-dichloro-2-methylpyrimidine 2-1 (8.2 g, 50.4 mmol) and Cs2CO3 (21.4 g, 65.7 mmol) were suspended in DMA (100 mL) and the mixture was stirred at 50° C. for 3 h. The mixture was cooled to rt, diluted with EtOAc (200 mL), and washed sequentially with water, brine, and water (150 mL each). The combined aqueous phase was back extracted with EtOAc (2×100 mL). The combined organic layer was dried over MgSO4, filtered, and concentrated to give a brownish solid. The solid was triturated with a diethyl ether/DCM mixture (95/5) and then filtered and dried under vacuum to give Intermediate 3 as a light brown solid (10.2 g, 74%). MS: m/z=314.2 (M+H).

Workup

temperatureThe mixture was cooled to rt
washwashed sequentially with water, brine, and water (150 mL each)
extractionThe combined aqueous phase was back extracted with EtOAc (2×100 mL)
dry with materialThe combined organic layer was dried over MgSO4
filtrationfiltered
concentrationconcentrated
customto give a brownish solid
customThe solid was triturated with a diethyl ether/DCM mixture (95/5)
filtrationfiltered
customdried under vacuum

Sources & evidence

ORD record: ord-ba894d7a913e4adc86ac85ed7ae624ed
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09365562B2

Reaction notes

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