Diisopropylethylamine → HCID 11540881, compound

HRID 2099371Notes

Reaction equation

HRID 2099371 reaction equation
Cl.Cl.[Cl:3][C:4]1[C:5]([F:30])=[C:6]([NH:10][C:11]2[C:20]3[C:15](=[CH:16][C:17]([O:23][CH:24]4[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]4)=[C:18]([O:21][CH3:22])[CH:19]=3)[N:14]=[CH:13][N:12]=2)[CH:7]=[CH:8][CH:9]=1.C(N(C(C)C)CC)(C)C.[CH3:40][O:41][CH2:42][CH2:43][O:44][CH2:45][C:46](Cl)=[O:47]>C(Cl)Cl>[Cl:3][C:4]1[C:5]([F:30])=[C:6]([NH:10][C:11]2[C:20]3[C:15](=[CH:16][C:17]([O:23][CH:24]4[CH2:29][CH2:28][N:27]([C:46](=[O:47])[CH2:45][O:44][CH2:43][CH2:42][O:41][CH3:40])[CH2:26][CH2:25]4)=[C:18]([O:21][CH3:22])[CH:19]=3)[N:14]=[CH:13][N:12]=2)[CH:7]=[CH:8][CH:9]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 70103382-(2-Methoxyethoxy)acetyl chlorideHCID 67415388HCID 67415388, compound

Product 1

HCID 11540881HCID 11540881, compoundYield 33.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

N-(3-Chloro-2-fluorophenyl)-6-methoxy-7-(piperidin-4-yloxy)quinazolin-4-amine dihydrochloride (300 mg), diisopropylethylamine (0.45 ml) and 2-(2-methoxyethoxy)acetyl chloride (0.105 g) were stirred in methylene chloride (9 ml) for 2.5 hours. Methylene chloride (20 ml) was added and the organic layer was washed with aqueous sodium hydroxide (2M, 30 ml) and water (30 ml). The resulting product was purified by flash column chromatography eluting with methanol (3%) and methylene chloride (97%) gave a foam. This was re-precipitated by stirring in diethyl ether (20 ml) to give the title product as a white solid (0.110 g); 1H NMR Spectrum: (DMSO d6 373K) 1.73 (m, 2H), 2.02 (m, 2H), 3.29 (s, 3H), 3.42 (m, 2H), 3.51 (t, J=7 Hz, 2H), 3.60 (t, J=9 Hz, 2H), 3.78 (m, 2H), 3.96 (s, 3H), 4.17 (s, 2H), 4.87 (m, 1H), 7.27 (m, 1H), 7.33 (s, 1H), 7.42 (m, 1H), 7.58 (m, 1H), 7.85 (s, 1H), 8.39 (s, 1H), 9.29 (br s, 1H); Mass Spectrum: (M+H)+ 519; melting point 110 to 111° C.

Workup

  1. washthe organic layer was washed with aqueous sodium hydroxide (2M, 30 ml) and water (30 ml)
  2. customThe resulting product was purified by flash column chromatography
  3. washeluting with methanol (3%) and methylene chloride (97%)
  4. customgave a foam
  5. customThis was re-precipitated

Sources & evidence

ORD record
ord-17e2de1c3d3c497db84b2b193d0d95e8
Source dataset
uspto-grants-2009_08
Patent number
US07569577B2

Reaction notes

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