Sodium Iodide → HCID 10391747, compound

HRID 1948911Notes

Reaction equation

HRID 1948911 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[CH2:39][CH2:38][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[CH2:39][CH2:38][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 31268PyrrolidineHCID 68519517HCID 68519517, compound

Product 1

HCID 10391747HCID 10391747, compound

Procedure

A suspension of 4-(3-chloro-2-fluoroanilino)-6-[1-(chloroacetyl)piperidin-4-yloxy]-7-methoxyquinazoline (0.15 g) (starting material used in Example 17) and sodium iodide (0.02 g) in pyrrolidine (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 eluting with increasingly polar mixtures of methylene chloride/methanol (100/0 to 92/8). The fractions containing the title product were combined and evaporated under vacuum and the residue triturated with diethyl ether, filtered and dried under vacuum to give the title product as a white crystalline solid. (0.085 g); 1H NMR Spectrum: (DMSO d6) 1.57-1.77 (m, 6H), 1.92-2.09 (m, 2H), 3.20-3.48 (m, 8H), 3.80-3.90 (m, 2H), 3.94 (s, 3H), 4.75 (m, 1H), 7.2-7.31 (m, 2H), 7.45-7.55 (m, 2H), 7.86 (s, 1H), 8.37 (s, 1H), 9.53 (s, 1H); Mass Spectrum: (M−H)+ 514.

Workup

  1. customThe mixture was evaporated under vacuum
  2. dissolutionthe residue dissolved in methylene chloride/methanol
  3. custompurified by column chromatography
  4. washeluting
  5. temperaturewith increasingly polar mixtures of methylene chloride/methanol (100/0 to 92/8)
  6. additionThe fractions containing the title product
  7. customevaporated under vacuum
  8. customthe residue triturated with diethyl ether
  9. filtrationfiltered
  10. customdried under vacuum

Sources & evidence

ORD record
ord-67808943f1d141e79723f2fdee0cd87d
Source dataset
uspto-grants-2013_03
Patent number
US08399667B2

Reaction notes

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