Morpholine → HCID 10393785, compound

HRID 1785176Notes

Reaction equation

HRID 1785176 reaction equation
[Br:1][C:2]1[CH:10]=[C:9]([C:11]#[C:12][CH:13]([O:15][CH3:16])[CH3:14])[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:30][CH2:31][CH2:32][CH2:33]Cl)=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1.[NH:35]1[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1>>[Br:1][C:2]1[CH:10]=[C:9]([C:11]#[C:12][CH:13]([O:15][CH3:16])[CH3:14])[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:30][CH2:31][CH2:32][CH2:33][N:35]3[CH2:40][CH2:39][O:38][CH2:37][CH2:36]3)=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1

Participants

3

Reactant 2

HCID 8083MorpholineHCID 68881835HCID 68881835, compound

Product 1

HCID 10393785HCID 10393785, compound

Procedure

A mixture of N-[5-bromo-7-(3-methoxybut-1-yn-1-yl)-1,3-benzodioxol-4-yl]-7-(3-chloropropoxy)-6-methoxyquinazolin-4-amine (0.12 g, 0.22 mmol) in morpholine (2 ml) was heated at 40 C for 5 hours and then stirred at room temperature overnight. The solvent was removed under reduced pressure and the residue purified directly by flash chromatography on silica eluting with increasingly polar solutions of methanol 0-8% in dichloromethane followed by trituration with diethyl ether to give the product as a racemate and in the form of a pale yellow solid (0.040 g). NMR Spectrum: (d6DMSO) 1.54 (d, 3H), 2.02-2.13 (m, 2H), 2.46-2.53 (m, 4H), 2.54-2.60 (m, 2H), 3.47 (s, 3H), 3.67-3.73 (m, 4H), 4.04 (s, 3H), 4.27-4.33 (m, 2H), 4.51 (q, 1H), 6.27 (s, 2H), 7.30 (s, 1H), 7.40 (s, 1H), 7.94 (s, 1H), 8.43 (s, 1H), 9.62 (s(broad), 1H). Mass Spectrum: M+H+ 599/601.

Workup

  1. temperaturewas heated at 40 C for 5 hours
  2. customThe solvent was removed under reduced pressure
  3. customthe residue purified directly by flash chromatography on silica eluting
  4. temperaturewith increasingly polar solutions of methanol 0-8% in dichloromethane
  5. customto give the product as a racemate

Sources & evidence

ORD record
ord-a0c39120b0024a4aacdfde0cb07287d5
Source dataset
uspto-grants-2009_03
Patent number
US07504408B2

Reaction notes

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