Acetic Acid → HCID 21847840, compound

HRID 618672Notes

Reaction equation

HRID 618672 reaction equation
[H-].[Na+].[OH:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][N:5]=1.Cl.[Cl:11][C:12]1[CH:13]=[C:14]([CH:27]=[CH:28][C:29]=1[Cl:30])[NH:15][C:16]1[C:25]2[C:20](=[CH:21][CH:22]=[C:23](F)[CH:24]=2)[N:19]=[CH:18][N:17]=1.C(O)(=O)C>CN1C(=O)CCC1>[Cl:11][C:12]1[CH:13]=[C:14]([CH:27]=[CH:28][C:29]=1[Cl:30])[NH:15][C:16]1[C:25]2[C:20](=[CH:21][CH:22]=[C:23]([N:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:4]3=[O:3])[CH:24]=2)[N:19]=[CH:18][N:17]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 24758Sodium hydrideHCID 21847841HCID 21847841, compoundHCID 178516071HCID 178516071, compound

Product 1

HCID 21847840HCID 21847840, compoundYield 51.8%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

Sodium hydride (0.24 g) was added to a solution of 2-hydroxypyridine (0.95 g) in NMP (10 ml) and the mixture was stirred at ambient temperature for 30 minutes. A mixture of a portion (3 ml) of the resultant solution and 4-(3,4-dichloroanilino)-6-fluoroquinazoline hydrochloride (0.172 g) was heated at 215° C. for 10 hours. The reaction mixture was acidified with glacial acetic acid and evaporated at 90° C. under high vacuum. The residue was chromatographed on silica using a mixture of methylene chloride and methanol, increasing in polarity from pure methylene chloride to a 19:1 mixture of methylene chloride: methanol as eluent. The product so obtained was triturated with a 1:1 mixture of isopropanol and ethyl acetate. The solid was filtered off, washed with ethyl acetate and dried under high vacuum to give 4-(3,4-dichloroanilino)-6-(2-oxo-1,2-dihydropyridin-1-yl)quinazoline (0.099 g); NMR Spectrum: (CD3SOCD3) 6.44 (m, 1H), 6.57 (m, 1H), 7.55-7.66 (m, 1H), 7.68 (d, 1H), 7.75-8.00 (m, 4H), 8.34 (d, 1H), 8.65 (s, 1H), 8.78 (s, 1H), 9.78 (s, 1H);

Workup

  1. temperaturewas heated at 215° C. for 10 hours
  2. customevaporated at 90° C. under high vacuum
  3. customThe residue was chromatographed on silica using
  4. additiona mixture of methylene chloride and methanol
  5. temperatureincreasing in polarity from pure methylene chloride to a 19:1 mixture of methylene chloride
  6. customThe product so obtained
  7. customwas triturated with a 1:1 mixture of isopropanol and ethyl acetate
  8. filtrationThe solid was filtered off
  9. washwashed with ethyl acetate
  10. customdried under high vacuum

Sources & evidence

ORD record
ord-c926bdee44b04f28996e2e5c871a604d
Source dataset
uspto-grants-1999_09
Patent number
US05955464

Reaction notes

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