Dichloromethane → 2-Aminomethyl-N4-(4-isopropoxy-phenyl)-N4-methyl-quinazoline-4,6-diamine

HRID 1876201Notes

Reaction equation

HRID 1876201 reaction equation
Cl[CH2:2][C:3]1[N:12]=[C:11]([N:13]([C:15]2[CH:20]=[CH:19][C:18]([O:21][CH:22]([CH3:24])[CH3:23])=[CH:17][CH:16]=2)[CH3:14])[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([N+:25]([O-])=O)[CH:9]=2)[N:4]=1.ClC1C2C(=CC=C([N+]([O-])=O)C=2)N=C(CCl)[N:30]=1.C(OC1C=CC(NC)=CC=1)(C)C.C(Cl)Cl>CC(O)C.Cl>[NH2:30][CH2:2][C:3]1[N:12]=[C:11]([N:13]([C:15]2[CH:20]=[CH:19][C:18]([O:21][CH:22]([CH3:24])[CH3:23])=[CH:17][CH:16]=2)[CH3:14])[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([NH2:25])[CH:9]=2)[N:4]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 18002910N-Methyl-4-[(propan-2-yl)oxy]anilineHCID 68518668(2-Chloromethyl-6-nitro-quinazolin-4-yl)-(4-isopropoxy-phenyl)-methyl-amineHCID 866400614-Chloro-2-chloromethyl-6-nitroquinazoline

Product 1

HCID 592420452-Aminomethyl-N4-(4-isopropoxy-phenyl)-N4-methyl-quinazoline-4,6-diamineYield 71%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidCatalystHCID 3776IsopropanolSolvent

Procedure

(2-Chloromethyl-6-nitro-quinazolin-4-yl)-(4-isopropoxy-phenyl)-methyl-amine: A suspension of 4-chloro-2-chloromethyl-6-nitroquinazoline (200 mg, 0.77 mmol) and (4-isopropoxy-phenyl)-methyl-amine (140 mg, 0.84 mmol) in i-PrOH (1.5 mL) was treated with HCl (12 M, 6 drops) and stirred at rt overnight. CH2Cl2 was added and the reaction washed with 5% NaOH, dried (MgSO4), filtered and concentrated. The residue was purified by gradient MPLC (SiO2, EtOAc/hexanes, 0-100%) to provide 203 mg (71%) of the title compound. 1H NMR (DMSO-d6) δ 8.35 (dd, 1H), 7.86 (dd, 1H), 7.71 (dd, 1H), 7.32-7.40 (m, 2H), 7.08-7.12 (m, 2H), 4.78 (s, 2H), 4.71 (sept, 1H), 3.63 (s, 3H), 1.31 (d, 6H); LC-MS (ESI+; 387 ([M+H]+)).

Workup

  1. washthe reaction washed with 5% NaOH
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by gradient MPLC (SiO2, EtOAc/hexanes, 0-100%)

Sources & evidence

ORD record
ord-d76e857a42884d8fa51fdaf5df954640
Source dataset
uspto-grants-2012_11
Patent number
US08309562B2

Reaction notes

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