(3-Methoxyphenyl)boronic acid → HCID 67297972, compound

HRID 1520374Notes

Reaction equation

HRID 1520374 reaction equation
I[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]1[CH:17]=[N:16][CH:15]=[CH:14][N:13]=1)[N:6]=[C:5]2[NH:18][CH3:19].[CH3:20][O:21][C:22]1[CH:23]=[C:24](B(O)O)[CH:25]=[CH:26][CH:27]=1.O.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[CH3:20][O:21][C:22]1[CH:27]=[C:26]([C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[N:8]=[C:7]([C:12]2[CH:17]=[N:16][CH:15]=[CH:14][N:13]=2)[N:6]=[C:5]3[NH:18][CH3:19])[CH:25]=[CH:24][CH:23]=1

Participants

7

Reactant 3

HCID 2734370(3-Methoxyphenyl)boronic acidHCID 22031701Potassium phosphate, tribasic, monohydrateHCID 67297986HCID 67297986, compound

Product 1

HCID 67297972HCID 67297972, compoundYield 26.5%

Reagents, catalysts & solvents 3

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

In a 50 ml, round-bottomed flask was added 6-iodo-N-methyl-2-(pyrazin-2-yl)quinazolin-4-amine (0.100 g, 0.275 mmol), 3-methoxyphenylboronic acid (0.063 g, 0.413 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine) dichloropalladium(II) (0.016 g, 0.022 mmol), and potassium phosphate tribasic monohydrate (0.190 g, 0.826 mmol) in dioxane (5 mL) and water (0.5 mL) to give a brown suspension. The reaction mixture was heated at 80° C. overnight under argon. After cooling to room temperature, the reaction mixture was diluted with water (10 mL) and then a precipitate formed. The resulting solid was collected by filtration and washed with ethyl acetate and dried to give 25 mg of 6-(3-methoxyphenyl)-N-methyl-2-(pyrazin-2-yl)quinazolin-4-amine as a pale yellow solid in a 26% yield. LCMS m/z=344 (M+1) (Method D) (retention time=1.43 ruin). 1H NMR (300 MHz, DMSO) δ 9.64 (s, 1H), 8.85-8.78 (m, 1H), 8.77-8.71 (m, 1H), 8.70-8.63 (m, 1H), 8.63-8.55 (m, 1H), 8.18 (d, J=8.8 Hz, 1H), 7.89 (d, J=8.9 Hz, 1H), 7.53-7.31 (m, 3H), 7.09-6.92 (m, 1H), 3.86 (5, 3H), 3.17 (d, J=3.6 Hz, 3H).

Workup

  1. customto give a brown suspension
  2. temperatureAfter cooling to room temperature
  3. customa precipitate formed
  4. filtrationThe resulting solid was collected by filtration
  5. washwashed with ethyl acetate
  6. customdried

Sources & evidence

ORD record
ord-12ed8db119de40a8b55a40098b23af8f
Source dataset
uspto-grants-2015_07
Patent number
US09073890B2

Reaction notes

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