Potassium Carbonate → N-{4-[(4-Methoxy-phenyl)-methyl-amino]-quinazolin-2-ylmethyl}-acetamide

HRID 1876190Notes

Reaction equation

HRID 1876190 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]([CH3:32])[C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[N:13]=[C:12]([CH2:20][N:21]3C(=O)C4[C:23](=CC=CC=4)[C:22]3=[O:31])[N:11]=2)=[CH:5][CH:4]=1.Cl.ClCC1N=C(N(C2C=CC(OC)=CC=2)C)C2C(=CC=CC=2)N=1.C([O-])([O-])=O.[K+].[K+].C1(=O)NC(=O)C2=CC=CC=C12.[K]>CN(C=O)C.CCOC(C)=O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([N:9]([CH3:32])[C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[N:13]=[C:12]([CH2:20][NH:21][C:22](=[O:31])[CH3:23])[N:11]=2)=[CH:7][CH:8]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 24194345Phthalimide potassium saltHCID 592372612-{4-[(4-Methoxy-phenyl)-methyl-amino]-quinazolin-2-ylmethyl}-isoindole-1,3-dioneHCID 68515345HCID 68515345, compound

Product 1

HCID 59242014N-{4-[(4-Methoxy-phenyl)-methyl-amino]-quinazolin-2-ylmethyl}-acetamideYield 68%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

2-{4-[(4-Methoxy-phenyl)-methyl-amino]-quinazolin-2-ylmethyl}-isoindole-1,3-dione: A suspension of (2-chloromethyl-quinazolin-4-yl)-(4-methoxy-phenyl)-methyl-amine hydrochloride (10.367 g, 16.2 mmol) and K2CO3 (2.25 g, 16.3 mmol) in DMF (50 mL) was heated to 70° C. for 1 h. The reaction was cooled to rt, potassium phthalimide (6.004 g, 32.5 mmol) was added and the reaction heated to 70° C. for 2 h. The reaction was cooled to rt, diluted with EtOAc, washed with H2O and 5% NaOH, dried (MgSO4), filtered and concentrated. The residue was purified by gradient MPLC (SiO2, EtOAc/hexanes 0-100%) to yield 8.56 g (68%) of the title compound. 1H NMR (DMSO-d6) δ 7.95-8.02 (m, 2H), 7.87-7.94 (m, 2H), 7.55-7.60 (m, 2H), 7.18-7.22 (m, 2H), 7.02-7.12 (m, 1H), 6.94-7.01 (m, 2H), 6.88 (dt, 1H), 4.95 (s, 2H), 3.77 (s, 3H), 3.26 (s, 3H); HRMS (ES) calcd for C25H21N4O3 (M+H) 425.1608, found 425.1604.

Workup

  1. temperatureThe reaction was cooled to rt
  2. temperaturethe reaction heated to 70° C. for 2 h
  3. temperatureThe reaction was cooled to rt
  4. washwashed with H2O and 5% NaOH
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by gradient MPLC (SiO2, EtOAc/hexanes 0-100%)

Sources & evidence

ORD record
ord-5318963e0ea4444aac8b214e037022df
Source dataset
uspto-grants-2012_11
Patent number
US08309562B2

Reaction notes

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