Sodium Carbonate → N-(4-methyl-3-nitrophenyl)-5-(4-(trifluoromethoxy)phenyl)pyrimidin-2-amine

HRID 2067880Notes

Reaction equation

Br[C:2]1[CH:3]=[N:4][C:5]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([CH3:15])=[C:11]([N+:16]([O-:18])=[O:17])[CH:10]=2)=[N:6][CH:7]=1.[F:19][C:20]([F:32])([F:31])[O:21][C:22]1[CH:27]=[CH:26][C:25](B(O)O)=[CH:24][CH:23]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:15][C:12]1[CH:13]=[CH:14][C:9]([NH:8][C:5]2[N:4]=[CH:3][C:2]([C:25]3[CH:24]=[CH:23][C:22]([O:21][C:20]([F:19])([F:31])[F:32])=[CH:27][CH:26]=3)=[CH:7][N:6]=2)=[CH:10][C:11]=1[N+:16]([O-:18])=[O:17]

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of 5-bromo-N-(4-methyl-3-nitrophenyl)pyrimidin-2-amine 27 (9.7 mmol) in 1,4-dioxane (29 mL) is added 4-(trifluoromethoxy)phenylboronic acid (10.7 mmol), Na2CO3 (29.2 mmol of 1.8 M aq. solution) and Pd(PPh3)4 (1.46 mmol). The reaction is evacuated and backfilled with nitrogen twice then heated at 100° C. for 12 h. The reaction mixture is diluted with water (20 mL) and extracted with EtOAc (2×50 mL). The organic layer is separated, dried over Na2SO4 and concentrated. Purification by preparative HPLC (ACN gradient 10-70%) affords N-(4-methyl-3-nitrophenyl)-5-(4-(trifluoromethoxy)phenyl)pyrimidin-2-amine 28b. MS (m/z) (M+1)+: 390.1.

Workup

customThe reaction is evacuated
additionThe reaction mixture is diluted with water (20 mL)
extractionextracted with EtOAc (2×50 mL)
customThe organic layer is separated
dry with materialdried over Na2SO4
concentrationconcentrated
customPurification by preparative HPLC (ACN gradient 10-70%)

Sources & evidence

ORD record: ord-d563aa7188984987b883d7af0f1f6b9c
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08293757B2

Reaction notes

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