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

HRID 2067878Notes

Reaction equation

HRID 2067878 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.FC(F)OC1C=CC(B2OC(C)(C)C(C)(C)O2)=CC=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:6]=[CH:7][CH:2]=[CH:3][N:4]=2)=[CH:10][C:11]=1[N+:16]([O-:18])=[O:17]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 220323032-(4-(Difluoromethoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 638723175-Bromo-N-(4-methyl-3-nitrophenyl)pyrimidin-2-amine

Product 1

HCID 86660119N-(4-methyl-3-nitrophenyl)pyrimidin-2-amine

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of 5-bromo-N-(4-methyl-3-nitrophenyl)pyrimidin-2-amine 27 (0.5 mmol) in 1,4-dioxane (2.0 mL) is added 2-(4-(difluoromethoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane 7 (0.5 mmol), Na2CO3 (1.5 mmol of a 3.0 M aq. solution) and Pd(PPh3)4 (0.025 mmol). The reaction is evacuated and backfilled with nitrogen twice then heated in the microwave oven at 150° C. for 10 min. The reaction mixture is diluted with water (10 mL) and extracted with DCM (2×50 mL). The organic layer is separated, dried over Na2SO4 and concentrated. Purification by preparative HPLC (ACN gradient 10-70%) affords 4-(difluoromethoxy)phenyl)-N-(4-methyl-3-nitrophenyl)pyrimidin-2-amine 28a. 1H NMR (400 MHz, d6-DMSO) δ 10.23 (s, 1H), 8.92 (s, 2H), 8.66 (d, J=2.4 Hz, 1H), 7.93 (dd, J=2.4, 8.4 Hz, 1H), 7.82 (d, J=8.4 Hz, 2H), 7.43 (d, J=8.4 Hz, 1H), 7.31 (t, J=74.0 Hz, 1H), 7.29 (d, J=8.4 Hz, 2H), 2.47 (s, 3H). MS (m/z) (M+1)+: 373.1.

Workup

  1. customThe reaction is evacuated
  2. additionThe reaction mixture is diluted with water (10 mL)
  3. extractionextracted with DCM (2×50 mL)
  4. customThe organic layer is separated
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customPurification by preparative HPLC (ACN gradient 10-70%)

Sources & evidence

ORD record
ord-eeee2035544a492996f8a3800c25e7e8
Source dataset
uspto-grants-2012_10
Patent number
US08293757B2

Reaction notes

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