Diisopropylethylamine → N2-(2-amino-ethyl)-N4-(3,4-dimethoxy-phenyl)-N4-methyl-quinazoline-2,4-diamine

HRID 1876186Notes

Reaction equation

HRID 1876186 reaction equation
C(OC(=O)[NH:7][CH2:8][CH2:9][NH:10][C:11]1[N:20]=[C:19]([N:21]([C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[C:25]([O:31][CH3:32])[CH:24]=2)[CH3:22])[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[N:12]=1)(C)(C)C.ClC1N=C(N(C2C=CC(OC)=C(OC)C=2)C)C2C(=CC=CC=2)N=1.C(N(C(C)C)C(C)C)C.C(OC(=O)NCCN)(C)(C)C>CCCCO>[NH2:7][CH2:8][CH2:9][NH:10][C:11]1[N:20]=[C:19]([N:21]([C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[C:25]([O:31][CH3:32])[CH:24]=2)[CH3:22])[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[N:12]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 187201N-BOC-ethylenediamineHCID 11771849(2-Chloro-quinazolin-4-yl)-(3,4-dimethoxy-phenyl)-methyl-amineHCID 59237286(2-{4-[(3,4-Dimethoxy-phenyl)-methyl-amino]-quinazolin-2-ylamino}-ethyl)-carbamic acid tert-butyl ester

Product 1

HCID 59242094N2-(2-amino-ethyl)-N4-(3,4-dimethoxy-phenyl)-N4-methyl-quinazoline-2,4-diamineYield 91%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

(2-{4-[(3,4-Dimethoxy-phenyl)-methyl-amino]-quinazolin-2-ylamino}-ethyl)-carbamic acid tert-butyl ester: A soln of (2-chloro-quinazolin-4-yl)-(3,4-dimethoxy-phenyl)-methyl-amine (440 mg, 1.33 mmol), ethyl-diisopropyl-amine (0.47 mL, 2.70 mmol) and (2-amino-ethyl)-carbamic acid tert-butyl ester (316 μL, 2.00 mmol) in n-BuOH (5 mL) was reacted at 110° C. for 29 h then concd on a rotary evaporator. The crude material was dissolved in CHCl3 (8 mL) then washed with satd NaHCO3 (2×3 mL) and water (1×3 mL). This soln was dried (MgSO4), filtered through a plug of silica with a wash of 100:10:1 CHCl3:MeOH:concd NH4OH, concentrated, then purified by MPLC (amine column (Isco 68-2203-101)/0-100% i-PrOH in CHCl3.), yielding the title compound as a tan solid (550 mg; 91%). 1H NMR (CDCl3) δ 7.46-7.35 (m, 2H), 6.90-6.82 (m, 2H), 6.77-6.66 (m, 3H), 5.80 (s(br), 1H), 5.44 (s(br), 1H), 3.92 (s, 3H), 3.79 (s, 3H), 3.68 (m, 2H), 3.53 (s, 3H), 3.44 (m, 2H), 1.44 (s, 9H); LC-MS (ESI+; 454 ([M+H]+)).

Workup

  1. customthen concd on a rotary evaporator
  2. dissolutionThe crude material was dissolved in CHCl3 (8 mL)
  3. washthen washed with satd NaHCO3 (2×3 mL) and water (1×3 mL)
  4. dry with materialThis soln was dried (MgSO4)
  5. filtrationfiltered through a plug of silica with
  6. washa wash of 100:10:1 CHCl3
  7. concentrationMeOH:concd NH4OH, concentrated
  8. custompurified by MPLC (amine column (Isco 68-2203-101)/0-100% i-PrOH in CHCl3.)

Sources & evidence

ORD record
ord-6fc12ee2a66040f3bc4603f4c5184a9a
Source dataset
uspto-grants-2012_11
Patent number
US08309562B2

Reaction notes

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