Potassium Carbonate → HCID 67140852, compound

HRID 2109800Notes

Reaction equation

HRID 2109800 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:10]=[N:11][C:12]([NH:15][C:16]3[CH:24]=[CH:23][C:19]([C:20]([OH:22])=[O:21])=[CH:18][CH:17]=3)=[N:13][CH:14]=2)=[CH:5][CH:4]=1.[CH3:25]OC(=O)C1C=CC(NC2N=CC(Br)=CN=2)=CC=1.B(O)(O)C1C=CC(OC)=CC=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.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>[CH3:25][O:21][C:20](=[O:22])[C:19]1[CH:23]=[CH:24][C:16]([NH:15][C:12]2[N:11]=[CH:10][C:9]([C:6]3[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=3)=[CH:14][N:13]=2)=[CH:17][CH:18]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 201262(4-Methoxyphenyl)boronic acidHCID 45789684Methyl 4-[(5-bromopyrimidin-2-yl)amino]benzoateHCID 57632633HCID 57632633, compound

Product 1

HCID 67140852HCID 67140852, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

4-[5-(4-Methoxy-phenyl)-pyrimidin-2-ylamino]-benzoic acid can be prepared by the following procedure. To a solution of 4-(5-bromo-pyrimidin-2-ylamino)-benzoic acid methyl ester (0.3 mmol) (from Example 3f) in DMF (1.5 mL) are added 4-methoxy boronic acid (0.3 mmol), aq K2CO3 (0.68 mmol) and Pd(PPh3)4 (0.16 mmol). The reaction mixture is evacuated twice and heated at 80° C. for 30 min. After this time the reaction mixture is diluted with a sat. aq NH4Cl and extracted with DCM (3×30 mL). The organic layer is washed with brine, dried over Na2SO4 and concentrated to afford 4-[5-(4-methoxy-phenyl)-pyrimidin-2-ylamino]-benzoic acid methyl ester that upon trituration with MeOH gives an orange solid (95%). MS (m/z) (M+1)+ 336.1. This solid is suspended in a 3:2:1=THE:MeOH:H2O solution (3 mL) and 6N LiOH (0.15 mL) added and stirred at rt for 12 h. At this point the solvent is removed and the residue is dissolved in water and extracted with DCM (3×30 mL). The mixture is adjusted to pH˜2 and extracted with a 3:1=DCM:IPA mixture (5×30 mL). The organic layer is washed with brine, dried over Na2SO4 and concentrated to afford 4-[5-(4-methoxy-phenyl)-pyrimidin-2-ylamino]-benzoic acid as an orange powder (100%) which is used without further purification. 1HNMR (400 MHz, DMSO-d6) δ 10.18 (s, 1H), 8.87 (s, 2H), 7.95-7.87 (m, 4H), 7.71 (d, J=8.0 Hz, 2H), 7.06 (d, J=8.0 Hz, 2H), 3.81 (s, 3H). MS (m/z) (M+1)+ 322.1.

Workup

  1. customThe reaction mixture is evacuated twice
  2. additionAfter this time the reaction mixture is diluted with a sat. aq NH4Cl
  3. extractionextracted with DCM (3×30 mL)
  4. washThe organic layer is washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-5c14aead081c4c7687d67c4e8965776f
Source dataset
uspto-grants-2009_04
Patent number
US07514447B2

Reaction notes

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