5-{(1R)-2-[allyl(methyl)amino]-1-methylethoxy}-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}quinazolin-4-amine → 5-[(1R)-1-methyl-2-(methylamino)ethoxy]-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}quinazolin-4-amine

HRID 1864333Notes

Reaction equation

HRID 1864333 reaction equation
[CH2:1]([N:4](C)[CH2:5][C@@H:6]([CH3:34])[O:7][C:8]1[CH:17]=[CH:16][CH:15]=[C:14]2[C:9]=1[C:10]([NH:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][C:26]3[CH:27]=[N:28][C:29]([CH3:32])=[CH:30][CH:31]=3)=[C:21]([CH3:33])[CH:20]=1)=[N:11][CH:12]=[N:13]2)C=C>C(#N)C.O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cl-].[Rh]>[CH3:34][C@@H:6]([O:7][C:8]1[CH:17]=[CH:16][CH:15]=[C:14]2[C:9]=1[C:10]([NH:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][C:26]3[CH:27]=[N:28][C:29]([CH3:32])=[CH:30][CH:31]=3)=[C:21]([CH3:33])[CH:20]=1)=[N:11][CH:12]=[N:13]2)[CH2:5][NH:4][CH3:1]

Participants

4

Reactant 1

HCID 690578815-{(1R)-2-[allyl(methyl)amino]-1-methylethoxy}-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}quinazolin-4-amine

Product 1

HCID 690612485-[(1R)-1-methyl-2-(methylamino)ethoxy]-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}quinazolin-4-amineYield 83%

Reagents, catalysts & solvents 2

HCID 84599Chlorotris(triphenylphosphine)rhodium(I)CatalystHCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

A mixture of 5-{(1R)-2-[allyl(methyl)amino]-1-methylethoxy}-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}quinazolin-4-amine (2.25 g, 4.8 mmol) and chlorotris(triphenylphosphine)rhodium(I) (463 mg, 0.48 ml) in acetonitrile—water (17 ml:3 ml) was heated at reflux for 3 hours. After cooling, the solvents were evaporated under vacuum. The residue was purified by chromatography on silica gel (eluant: 2 to 4% methanol in DCM) to give 5-[(1R)-1-methyl-2-(methylamino)ethoxy]-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}quinazolin-4-amine (1.70 g, 83%); Mass spectrum: MH+ 430.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 3 hours
  3. temperatureAfter cooling
  4. customthe solvents were evaporated under vacuum
  5. customThe residue was purified by chromatography on silica gel (eluant: 2 to 4% methanol in DCM)

Sources & evidence

ORD record
ord-a41be052e17b4b7db137c408deddcfbd
Source dataset
uspto-grants-2009_12
Patent number
US07625908B2

Reaction notes

Loading…