Cesium carbonate → 4-(Azetidin-1-yl)-6-((cyclopropylmethoxy)methyl)-N-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)pyrimidin-2-amine

HRID 59132Notes

Reaction equation

[N:1]1([C:5]2[CH:10]=[C:9]([CH2:11][O:12][CH2:13][CH:14]3[CH2:16][CH2:15]3)[N:8]=[C:7](Cl)[N:6]=2)[CH2:4][CH2:3][CH2:2]1.[CH3:18][O:19][C:20]1[CH:21]=[C:22]([CH:24]=[CH:25][C:26]=1[N:27]1[CH:31]=[C:30]([CH3:32])[N:29]=[CH:28]1)[NH2:23].C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[N:1]1([C:5]2[CH:10]=[C:9]([CH2:11][O:12][CH2:13][CH:14]3[CH2:16][CH2:15]3)[N:8]=[C:7]([NH:23][C:22]3[CH:24]=[CH:25][C:26]([N:27]4[CH:31]=[C:30]([CH3:32])[N:29]=[CH:28]4)=[C:20]([O:19][CH3:18])[CH:21]=3)[N:6]=2)[CH2:4][CH2:3][CH2:2]1

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 4-(azetidin-1-yl)-2-chloro-6-((cyclopropylmethoxy)methyl)pyrimidine (44 mg, 0.17 mmol), 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline (42 mg, 0.21 mmol), cesium carbonate (113 mg, 0.35 mmol), palladium acetate (5.84 mg, 0.03 mmol) and 2-(dicyclohexyl-phosphino)biphenyl (9 mg, 0.03 mmol) in dioxane (2 mL) was stirred under argon at 120° C. for 90 minutes in microwave reactor. The mixture was filtered through a short silica plug which was washed with 10% MeOH in EtOAc (75 mL). The solvent was removed in vacuum and the residue was purified by preparative HPLC to give the title compound as a solid 56 mg (77%).

Workup

filtrationThe mixture was filtered through a short silica plug which
washwas washed with 10% MeOH in EtOAc (75 mL)
customThe solvent was removed in vacuum
customthe residue was purified by preparative HPLC

Sources & evidence

ORD record: ord-c9f9b316cee84999b5e317249fd4e278
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09439904B2

Reaction notes

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