Hydrochloric Acid → N-(6-chloro-1-benzofuran-7-yl)-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-amine

HRID 22776Notes

Reaction equation

HRID 22776 reaction equation
[Na].C[Si](C)(C)N[Si](C)(C)C.[NH2:11][C:12]1[C:20]2[O:19][CH:18]=[CH:17][C:16]=2[CH:15]=[CH:14][C:13]=1[Cl:21].Cl[C:23]1[C:32]2[C:27](=[CH:28][C:29]([O:35][CH2:36][CH2:37][CH2:38][N:39]3[CH2:44][CH2:43][O:42][CH2:41][CH2:40]3)=[C:30]([O:33][CH3:34])[CH:31]=2)[N:26]=[CH:25][N:24]=1.Cl>CN(C=O)C.C(Cl)Cl.C(O)(C)C.C(OCC)C>[Cl:21][C:13]1[CH:14]=[CH:15][C:16]2[CH:17]=[CH:18][O:19][C:20]=2[C:12]=1[NH:11][C:23]1[C:32]2[C:27](=[CH:28][C:29]([O:35][CH2:36][CH2:37][CH2:38][N:39]3[CH2:40][CH2:41][O:42][CH2:43][CH2:44]3)=[C:30]([O:33][CH3:34])[CH:31]=2)[N:26]=[CH:25][N:24]=1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 13838HexamethyldisilazaneHCID 5360545SodiumHCID 118239414-Chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolineHCID 221407936-Chloro-1-benzofuran-7-amine

Product 1

HCID 5330180N-(6-chloro-1-benzofuran-7-yl)-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-amineYield 85%

Reagents, catalysts & solvents 4

HCID 3283Diethyl EtherSolventHCID 3776IsopropanolSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

The sodium salt of 1,1,1,3,3,3-hexamethyldisilazane (1M solution in THF; 0.592 ml) was added to a solution of 7-amino-6-chlorobenzofuran (0.099 g) in DMF (5 ml) and the reaction mixture was stirred at ambient temperature for 30 minutes. 4-Chloro-6-methoxy-7-(3-morpholinopropoxy)quinazoline (0.1 g) was added and the resultant mixture was stirred at ambient temperature for 3 hours. The mixture was partitioned between ethyl acetate and water. The organic phase was washed in turn with water and brine, dried over magnesium sulphate and evaporated. The residue was purified by column chromatography on silica using increasingly polar mixtures of methylene chloride and methanol as eluent. The material so obtained was dissolved in methylene chloride and a 5M solution of hydrogen chloride gas in isopropanol (0.088 ml) was added. Diethyl ether was added and the precipitate was isolated and dried under vacuum. There was thus obtained the title compound (0.118 g) as a dihydrochloride salt; NMR Spectrum: (DMSOd6 and CF3CO2D) 2.35 (m, 2H), 3.15 (m, 2H), 3.35 (m, 2H), 3.55 (d, 2H), 3.75 (t, 2H), 4.0 (m, 2H), 4.05 (s, 3H), 4.35 (t, 2H), 7.15 (d, 1H), 7.45 (s, 1H), 7.55 (d, 1H), 7.8 (d, 1H), 8.1 (d, 1H), 8.25 (s, 1H), 8.8 (s, 1H); Mass Spectrum: M+H+ 469.

Workup

  1. customThe mixture was partitioned between ethyl acetate and water
  2. washThe organic phase was washed in turn with water and brine
  3. dry with materialdried over magnesium sulphate
  4. customevaporated
  5. customThe residue was purified by column chromatography on silica using
  6. temperatureincreasingly polar mixtures of methylene chloride and methanol as eluent
  7. customThe material so obtained
  8. customthe precipitate was isolated
  9. customdried under vacuum

Sources & evidence

ORD record
ord-e2974298fd2b4a36899cd4eb66ffae81
Source dataset
uspto-grants-2005_02
Patent number
US06849625B2

Reaction notes

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