Sodium Iodide → HCID 9984456, compound

HRID 1948910Notes

Reaction equation

HRID 1948910 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+].[NH:35]1[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1>>[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:35]4[CH2:40][CH2:39][O:38][CH2:37][CH2:36]4)[CH2:19][CH2:18]3)[CH:14]=2)[N:9]=[CH:8][N:7]=1

Participants

4

Reactant 3

HCID 5238Sodium IodideHCID 8083MorpholineHCID 68519517HCID 68519517, compound

Product 1

HCID 9984456HCID 9984456, compound

Procedure

A suspension of 4-(3-chloro-2-fluoroanilino)-6-[1-(chloroacetyl)piperidin-4-yloxy]-7-methoxyquinazoline (0.15 g) (starting material for Example 17) and sodium iodide (0.02 g) in morpholine (5 ml) was stirred at ambient temperature for 16 hours. The mixture was evaporated under vacuum and the residue dissolved in methylene chloride/methanol. This was adsorbed onto silica and purified by column chromatography on silica eluting with increasingly polar mixtures of methylene chloride/methanol (100/0 to 90/10). The fractions containing the title product were combined and evaporated under vacuum. The residue was triturated with diethylether, filtered and dried under vacuum to give the title product as a beige crystalline solid (0.105 g); 1H NMR Spectrum: (DMSO d6 and CD3COOD) 1.57-1.80 (m, 2H), 1.91-2.12 (m, 2H), 2.40-2.51 (m, 4H), 3.14-3.48 (m, 4H), 3.52-3.61 (m, 4H), 3.81-3.90 (m, 2H), 3.94 (s, 3H), 4.76 (m, 1H), 7.20-7.30 (m, 2H), 7.42-7.54 (m, 2H), 7.85 (s, 1H), 8.36 (s, 1H); Mass Spectrum: (M+H)+ 530.

Workup

  1. customThe mixture was evaporated under vacuum
  2. dissolutionthe residue dissolved in methylene chloride/methanol
  3. custompurified by column chromatography on silica eluting
  4. temperaturewith increasingly polar mixtures of methylene chloride/methanol (100/0 to 90/10)
  5. additionThe fractions containing the title product
  6. customevaporated under vacuum
  7. customThe residue was triturated with diethylether
  8. filtrationfiltered
  9. customdried under vacuum

Sources & evidence

ORD record
ord-2ddb315f13c7413bb3c067e4e90803be
Source dataset
uspto-grants-2013_03
Patent number
US08399667B2

Reaction notes

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