Potassium Carbonate → HCID 51030830, compound

HRID 2036788Notes

Reaction equation

HRID 2036788 reaction equation
Cl[C:2]1[N:11]=[C:10]([NH:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][C:8]=2[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[N:3]=1.[CH3:26][O:27][C:28]1[N:33]=[CH:32][C:31](B(O)O)=[CH:30][N:29]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O.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>[CH3:26][O:27][C:28]1[N:33]=[CH:32][C:31]([C:2]2[N:11]=[C:10]([NH:12][CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=3)[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][C:8]=3[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[N:3]=2)=[CH:30][N:29]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27367782-Methoxypyrimidine-5-boronic acidHCID 866706132-chloro-5-phenyl-N-(pyridin-2-ylmethyl)quinazolin-4-amine

Product 1

HCID 51030830HCID 51030830, compoundYield 56%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 2-chloro-5-phenyl-N-(pyridin-2-ylmethyl)quinazolin-4-amine (300 mg, 0.87 mmol) in DMF (20 mL) and H2O (2 mL) under nitrogen was added 2-methoxypyrimidin-5-ylboronic acid (199 mg, 1.30 mmol) and potassium carbonate (239 mg, 1.73 mmol). The resulting mixture was degassed with nitrogen for 15 min and then tetrakis(triphenylphosphine)palladium (100 mg, 0.086 mmol) was added. Upon completion of addition, the reaction mixture was again degassed with nitrogen for 10 min. After this time, the reaction mixture was heated to 90° C. where it stirred for 12 h. After this time, the reaction mixture was allowed to cool to room temperature and then quenched by the addition of water. The reaction mixture was extracted with ethyl acetate and the organic layer was washed successively with water and brine. The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure. The resulting concentrate was purified by preparative HPLC to afford 2-(2-methoxypyrimidin-5-yl)-5-phenyl-N-(pyridin-2-ylmethyl)quinazolin-4-amine (205 mg) as an off-white solid. Preparative HPLC Conditions: Column: Sunfire C18 (250×19 mm), Mobile Phase A: 0.1% TFA in H2O, Mobile Phase B: CH3CN, Gradient: 0 to 40% B over 35 min, 100% B for 10 min., Flow Rate: 14 mL/min., Retention time: 28 min. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 9.50 (s, 2H), 8.27 (d, J=4.7 Hz, 1H), 7.92 (d, J=3.6 Hz, 2H), 7.85-7.81 (t, J=8.0 Hz, 1H), 7.60-7.52 (m, 5H), 7.42-7.38 (m, 2H), 7.34-7.31 (m, 1H), 4.83 (d, J=4.2 Hz, 2H), 4.04 (s, 3H). LCMS Method O: retention time 1.45 min, [M+1]=421.2. HPLC Method B: purity 98.7%, retention time 5.53 min.

Workup

  1. customThe resulting mixture was degassed with nitrogen for 15 min
  2. additionUpon completion of addition
  3. customthe reaction mixture was again degassed with nitrogen for 10 min
  4. temperatureto cool to room temperature
  5. customquenched by the addition of water
  6. extractionThe reaction mixture was extracted with ethyl acetate
  7. washthe organic layer was washed successively with water and brine
  8. dry with materialThe combined organic layers were dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. concentrationThe resulting concentrate
  12. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-4a4dd87635ff47bbb069097bec0ab160
Source dataset
uspto-grants-2013_11
Patent number
US08575184B2

Reaction notes

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