Diisopropylethylamine → N-[5-chloro-7-(3-methoxyprop-1-yn-1-yl)-1,3-benzodioxol-4-yl]-7-{3-[4-(2-fluoroethyl)piperazin-1-yl]propoxy}-6-methoxyquinazolin-4-amine

HRID 1785182Notes

Reaction equation

HRID 1785182 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]([C:11]#[C:12][CH2:13][O:14][CH3:15])[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH:16][C:17]1[C:26]2[C:21](=[CH:22][C:23]([O:29][CH2:30][CH2:31][CH2:32]Cl)=[C:24]([O:27][CH3:28])[CH:25]=2)[N:20]=[CH:19][N:18]=1.[F:34][CH2:35][CH2:36][N:37]1[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1.C(N(C(C)C)CC)(C)C>COCCO.ClCCl>[Cl:1][C:2]1[CH:10]=[C:9]([C:11]#[C:12][CH2:13][O:14][CH3:15])[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH:16][C:17]1[C:26]2[C:21](=[CH:22][C:23]([O:29][CH2:30][CH2:31][CH2:32][N:40]3[CH2:41][CH2:42][N:37]([CH2:36][CH2:35][F:34])[CH2:38][CH2:39]3)=[C:24]([O:27][CH3:28])[CH:25]=2)[N:20]=[CH:19][N:18]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 210826721-(2-Fluoroethyl)piperazineHCID 68882624N-[5-chloro-7-(3-methoxyprop-1-yn-1-yl)-1,3-benzodioxol-4-yl]-7-(3-chloropropoxy)-6-methoxyquinazolin-4-amine

Product 1

HCID 11758051N-[5-chloro-7-(3-methoxyprop-1-yn-1-yl)-1,3-benzodioxol-4-yl]-7-{3-[4-(2-fluoroethyl)piperazin-1-yl]propoxy}-6-methoxyquinazolin-4-amineYield 46.7%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 80192-MethoxyethanolSolvent

Conditions

Temperature
110 °C

Procedure

N-[5-chloro-7-(3-methoxyprop-1-yn-1-yl)-1,3-benzodioxol-4-yl]-7-(3-chloropropoxy)-6-methoxyquinazolin-4-amine (0.165 g) was dissolved in 2-methoxyethanol (5 ml) and then fluoroethyl piperazine (0.821 g) was added followed by diisopropylethylamine (0.83 ml) and the mixture heated to 110° C. for 15 hours. The reaction mixture was cooled to room temperature, diluted with dichloromethane, washed with water and brine, dried over magnesium sulfate and then evaporated. The residue was purified by column chromatography on silica using increasingly polar mixtures of dichloromethane and methanol with methanolic ammonia as eluent. There was thus obtained the title compound (0.092 g) as a white powder, contaminated with approximately 5 wt. % diisopropylethylamine; NMR Spectrum: (CDCl3) 2.15 (quin, 2H), 2.63 (m(broad), 12H, ), 2.69 (t, 1H), 2.76 (t, 1H), 3.46 (s, 3H), 3.99 (s, 3H), 4.35 (s, 2H), 4.52 (t, 1H), 4.64 (t, 1H), 6.07 (s, 2H), 6.96 (s, 1H), 7.07 (s, 1H), 7.12 (s, 1H), 7.28 (s, 1H), 8.62 (s, 1H); Mass Spectrum: M+H+ 586/588.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. washwashed with water and brine
  3. dry with materialdried over magnesium sulfate
  4. customevaporated
  5. customThe residue was purified by column chromatography on silica using
  6. temperatureincreasingly polar mixtures of dichloromethane and methanol with methanolic ammonia as eluent

Sources & evidence

ORD record
ord-58cc892b556e4fe9a7a58be9f1319caf
Source dataset
uspto-grants-2009_03
Patent number
US07504408B2

Reaction notes

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