Dimethylamine → HCID 10368199, compound

HRID 1948907Notes

Reaction equation

HRID 1948907 reaction equation
[Cl:1][C:2]1[C:3]([F:32])=[C:4]([CH:29]=[CH:30][CH:31]=1)[NH:5][C:6]1[C:15]2[C:10](=[CH:11][C:12]([O:27][CH3:28])=[C:13]([O:16][CH:17]3[CH2:22][CH2:21][N:20]([C:23](=[O:26])[CH2:24]Cl)[CH2:19][CH2:18]3)[CH:14]=2)[N:9]=[CH:8][N:7]=1.[I-].[Na+].[CH3:35][NH:36][CH3:37]>>[Cl:1][C:2]1[C:3]([F:32])=[C:4]([CH:29]=[CH:30][CH:31]=1)[NH:5][C:6]1[C:15]2[C:10](=[CH:11][C:12]([O:27][CH3:28])=[C:13]([O:16][CH:17]3[CH2:22][CH2:21][N:20]([C:23](=[O:26])[CH2:24][N:36]([CH3:37])[CH3:35])[CH2:19][CH2:18]3)[CH:14]=2)[N:9]=[CH:8][N:7]=1

Participants

4

Reactant 3

HCID 674DimethylamineHCID 5238Sodium IodideHCID 68519517HCID 68519517, compound

Product 1

HCID 10368199HCID 10368199, compound

Procedure

A suspension of 4-(3-chloro-2-fluoroanilino)-6-[1-(chloroacetyl)piperidin-4-yloxy]-7-methoxyquinazoline (0.14 g) and sodium iodide (0.1 g) in an ethanolic solution of dimethylamine (33%) (10 ml) was stirred at ambient temperature for 2 hours. The mixture was evaporated under vacuum and the residue dissolved in methylene chloride and purified by column chromatography on silica eluting with increasingly polar mixtures of methylene chloride/methanol (saturated with ammonia) (100/0 to 85/15). The fractions containing the title product were combined and evaporated under vacuum and the residue triturated with diethyl ether and filtered to give the title product as a crystalline solid (0.085 g); 1H NMR Spectrum: (DMSO d6) 1.56-1.78 (m, 2H), 1.92-2.08 (m, 2H), 2.20 (s, 6H), 3.05-3.18 (m, 2H), 3.30-3.48 (m, 2H), 3.79-3.90 (m, 2H), 3.94 (s, 3H), 4.75 (m, 1H), 7.21 (s, 1H), 7.28 (t, 1H), 7.44-7.56 (m, 2H), 7.86 (s, 1H), 8.37 (s, 1H), 9.53 (s, 1H); Mass Spectrum: (M+H)+ 488.

Workup

  1. customThe mixture was evaporated under vacuum
  2. dissolutionthe residue dissolved in methylene chloride
  3. custompurified by column chromatography on silica eluting
  4. temperaturewith increasingly polar mixtures of methylene chloride/methanol (saturated with ammonia) (100/0 to 85/15)
  5. additionThe fractions containing the title product
  6. customevaporated under vacuum
  7. customthe residue triturated with diethyl ether
  8. filtrationfiltered

Sources & evidence

ORD record
ord-5df5c8f884274d65b43f15381c489838
Source dataset
uspto-grants-2013_03
Patent number
US08399667B2

Reaction notes

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