Trifluoroacetic acid → HCID 60036696, compound

HRID 1948920Notes

Reaction equation

HRID 1948920 reaction equation
FC(F)(F)C(O)=O.[Cl:8][C:9]1[C:10]([F:46])=[C:11]([CH:43]=[CH:44][CH:45]=1)[NH:12][C:13]1[C:22]2[C:17](=[CH:18][C:19]([O:41][CH3:42])=[C:20]([O:23][C@@H:24]3[CH2:28][N:27](C(OC(C)(C)C)=O)[C@H:26]([C:36](=[O:40])[N:37]([CH3:39])[CH3:38])[CH2:25]3)[CH:21]=2)[N:16]=[CH:15][N:14]=1>C(Cl)Cl>[Cl:8][C:9]1[C:10]([F:46])=[C:11]([CH:43]=[CH:44][CH:45]=1)[NH:12][C:13]1[C:22]2[C:17](=[CH:18][C:19]([O:41][CH3:42])=[C:20]([O:23][C@@H:24]3[CH2:28][NH:27][C@H:26]([C:36](=[O:40])[N:37]([CH3:39])[CH3:38])[CH2:25]3)[CH:21]=2)[N:16]=[CH:15][N:14]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 60036687HCID 60036687, compound

Product 1

HCID 60036696HCID 60036696, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (5 ml) was added to a solution of 4-(3-chloro-2-fluoroanilino)-6-[(2S,4S)-1-(tert-butoxycarbonyl)-2-(N,N-dimethylcarbamoyl)pyrrolidin-4-yloxy]-7-methoxyquinazoline (0.17 g) in methylene chloride (10 ml) and the reaction mixture was stirred at ambient temperature for 2 hours. The reaction mixture was evaporated under vacuum and the residue dissolved in methanol (saturated with ammonia)/methylene chloride, adsorbed onto silica and purified by column chromatography eluting with increasingly polar mixtures of methylene chloride/methanol (saturated with ammonia) (100/0 to 85/15). The fractions containing the required product were combined and evaporated under vacuum to give the title product as a colourless gum which crystallised on standing (0.13 g); 1H NMR Spectrum: (DMSO d6 and CD3COOD) 1.85-1.96 (m, 1H), 2.84-2.95 (m, 4H), 3.00 (s, 3H), 3.24-332 (m, 1H), 3.40-3.48 (m, 1H), 3.95 (s, 3H), 4.31 (m, 1H), 5.21 (m, 1H), 7.20-7.30 (m, 2H), 7.47-7.55 (m, 2H), 7.76 (s, 1H), 8.37 (s, 1H); Mass Spectrum: (M+H)+ 460.

Workup

  1. customThe reaction mixture was evaporated under vacuum
  2. dissolutionthe residue dissolved in methanol (saturated with ammonia)/methylene chloride
  3. custompurified by column chromatography
  4. washeluting
  5. temperaturewith increasingly polar mixtures of methylene chloride/methanol (saturated with ammonia) (100/0 to 85/15)
  6. additionThe fractions containing the required product
  7. customevaporated under vacuum

Sources & evidence

ORD record
ord-c325c427f87a426e931bac88b5325c94
Source dataset
uspto-grants-2013_03
Patent number
US08399667B2

Reaction notes

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