Dichloromethane → 5-(4-(4-(6-Methylpyridin-3-yloxy)-3-methylphenylamino)quinazolin-6-yl)furan-2-carbaldehyde

HRID 877097Notes

Reaction equation

HRID 877097 reaction equation
[CH3:1][C:2]1[N:7]=[CH:6][C:5]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]3[C:25]4[C:20](=[CH:21][CH:22]=[C:23](I)[CH:24]=4)[N:19]=[CH:18][N:17]=3)=[CH:11][C:10]=2[CH3:27])=[CH:4][CH:3]=1.[C:28]([O-:31])([O-])=O.[K+].[K+].[CH2:34](Cl)Cl.CO[CH2:39][CH2:40][O:41][CH3:42]>C(O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:1][C:2]1[N:7]=[CH:6][C:5]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]3[C:25]4[C:20](=[CH:21][CH:22]=[C:23]([C:42]5[O:41][C:40]([CH:28]=[O:31])=[CH:39][CH:34]=5)[CH:24]=4)[N:19]=[CH:18][N:17]=3)=[CH:11][C:10]=2[CH3:27])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 80711,2-DimethoxyethaneHCID 11430Potassium CarbonateHCID 11282772(6-Iodo-quinazolin-4-yl)-[3-methyl-4-(6-methyl-pyridin-3-yloxy)-phenyl]-amine

Product 1

HCID 866684775-(4-(4-(6-Methylpyridin-3-yloxy)-3-methylphenylamino)quinazolin-6-yl)furan-2-carbaldehydeYield 98%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 702EthanolSolvent

Conditions

Temperature
75 °C

Procedure

Under nitrogen atmosphere, Pd(dppf)2Cl2 (85 mg) was added to a mixture of N-(4-(6-methylpyridin-3-yloxy)-3-methylphenyl)-6-iodoquinazolin-4-amine (468 mg, 1 mmole), 5-formylfuran-2-yl-2-boronic acid (170 mg) and 2M K2CO3 (4 mL) in Ethanol (4 mL) and DME (4 mL). The reaction mixture was heated at 75° C. for 4 h and cooled down to room temperature. Methylene chloride (30 mL) was added and washed with water and brine. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by flash chromatography, eluting with 20% methanol in dichloromethane to give the desired product as white solid (430 mg). LCMS ESI(+) m/z: 437 (M+1). Yield: 98%.

Workup

  1. temperaturecooled down to room temperature
  2. washwashed with water and brine
  3. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography
  7. washeluting with 20% methanol in dichloromethane

Sources & evidence

ORD record
ord-50713bc4d77344d6bf31dda6007e9482
Source dataset
uspto-grants-2015_03
Patent number
US08987284B2

Reaction notes

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