Acetic Anhydride → HCID 60036691, compound

HRID 1948945Notes

Reaction equation

HRID 1948945 reaction equation
[Cl:1][C:2]1[C:3]([F:27])=[C:4]([CH:24]=[CH:25][CH:26]=1)[NH:5][C:6]1[C:15]2[C:10](=[CH:11][C:12]([O:22][CH3:23])=[C:13]([O:16][C@@H:17]3[CH2:21][CH2:20][NH:19][CH2:18]3)[CH:14]=2)[N:9]=[CH:8][N:7]=1.[C:28](OC(=O)C)(=[O:30])[CH3:29]>C(Cl)Cl.N1C=CC=CC=1.C(N(C(C)C)CC)(C)C>[Cl:1][C:2]1[C:3]([F:27])=[C:4]([CH:24]=[CH:25][CH:26]=1)[NH:5][C:6]1[C:15]2[C:10](=[CH:11][C:12]([O:22][CH3:23])=[C:13]([O:16][C@@H:17]3[CH2:21][CH2:20][N:19]([C:28](=[O:30])[CH3:29])[CH2:18]3)[CH:14]=2)[N:9]=[CH:8][N:7]=1

Participants

6

Reactant 2

HCID 7918Acetic AnhydrideHCID 68522949HCID 68522949, compound

Product 1

HCID 60036691HCID 60036691, compoundYield 55%

Reagents, catalysts & solvents 3

HCID 1049PyridineSolventHCID 6344DichloromethaneSolventHCID 81531DiisopropylethylamineSolvent

Procedure

4-(3-chloro-2-fluoroanilino)-6-[(3R)-pyrrolidin-3-yloxy]-7-methoxyquinazoline (0.22 g, 0.51 mmole) (prepared as described in Example 29-preparation of starting materials) was dissolved in a mixture of methylene chloride (4 ml), pyridine (1 ml) and diisopropylethylamine (0.17 ml) under a nitrogen atmosphere. Acetic anhydride (0.1 ml, 1.0 mmole) was added and the mixture stirred at ambient temperature for 3 hours. The mixture was then partitioned between saturated aqueous NaHCO3 and ethyl acetate. The organic layer was separated, washed with brine, dried over Na2SO4, filtered and evaporated. The residue was purified by column chromatography eluting with methylene chloride/methanol (saturated with ammonia) (96/4). The fractions containing the expected product were evaporated and triturated with diethylether. The solid was filtered and dried under vacuum to give the title product as a white solid (0.12 g: 55%); 1H NMR Spectrum: (DMSO d6) 1.95-1.98 (m, 3H); 2.14-2.40 (m, 2H); 3.53-3.70 (m, 3H); 3.91 (m, 4H); 5.12-5.21 (m, 1H); 7.15-7.30 (m, 2H); 7.4-7.60 (m, 2H); 7.70-7.90 (m, 1H); 8.36-8.37 (d, 1H); 9.60-9.62 (m, 1H); Mass Spectrum: (M+H)+ 431.

Workup

  1. customThe mixture was then partitioned between saturated aqueous NaHCO3 and ethyl acetate
  2. customThe organic layer was separated
  3. washwashed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by column chromatography
  8. washeluting with methylene chloride/methanol (saturated with ammonia) (96/4)
  9. additionThe fractions containing the expected product
  10. customwere evaporated
  11. customtriturated with diethylether
  12. filtrationThe solid was filtered
  13. customdried under vacuum

Sources & evidence

ORD record
ord-ecf2961b877148738d0b3f013939d3f0
Source dataset
uspto-grants-2013_03
Patent number
US08399667B2

Reaction notes

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