Pyrrolidine → 2-Amino-7-(4-fluoro-phenyl)-4-methyl-7,8-dihydro-6H-quinazolin-5-one

HRID 2046466Notes

Reaction equation

HRID 2046466 reaction equation
[C:1]([CH:4]1[C:9](=[O:10])[CH2:8][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)[CH2:6][C:5]1=O)(=O)[CH3:2].N1CCCC1.C(=O)(O)O.[NH2:28][C:29]([NH2:31])=[NH:30]>C(Cl)(Cl)Cl.O1CCOCC1>[NH2:31][C:29]1[N:30]=[C:1]([CH3:2])[C:4]2[C:9](=[O:10])[CH2:8][CH:7]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[CH2:6][C:5]=2[N:28]=1

Participants

6

Reactant 3

HCID 31268PyrrolidineHCID 286947Carbonic acid-guanidine (1:1)HCID 529508832-Acetyl-5-(4-fluoro-phenyl)cyclohexane-1,3-dione2×

Product 1

HCID 172212082-Amino-7-(4-fluoro-phenyl)-4-methyl-7,8-dihydro-6H-quinazolin-5-one

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 312751,4-DioxaneSolvent

Procedure

To a stirred solution of 2-acetyl-5-(4-fluoro-phenyl)-cyclohexane-1,3-dione (200 mg, 0.80 mmol) from stage 1, in chloroform was added pyrrolidine (68 mg, 0.96 mmol). The reaction mixture was stirred at ambient temperature and monitored by TLC until complete disappearance of 2-acetyl-5-(4-fluoro-phenyl)cyclohexane-1,3-dione. The reaction mixture was washed with water (10 ml) and the solvent was removed under reduced pressure to give a solid m=229 mg, mass spectrum (ES-MS (+ve)) 302 [MH]+, Retention time 1.44 min, 100% UV. To a stirred solution of this solid (229 mg, 0.76 mmol) in dioxane (2.5 ml) was added guanidine carbonate (504 mg, 2.8 mmol) and the mixture heated at 100° C. and stirred for 16 h. 1,4-Dioxane was removed by evaporation under reduced pressure, water (5 ml) was added and the resulting precipitate was filtered, washed with water and heptane and air dried.

Workup

  1. washThe reaction mixture was washed with water (10 ml)
  2. customthe solvent was removed under reduced pressure
  3. customto give a solid m=229 mg, mass spectrum (ES-MS (+ve)) 302 [MH]+, Retention time 1.44 min, 100% UV
  4. temperaturethe mixture heated at 100° C.
  5. stirringstirred for 16 h
  6. custom1,4-Dioxane was removed by evaporation under reduced pressure, water (5 ml)
  7. additionwas added
  8. filtrationthe resulting precipitate was filtered
  9. washwashed with water and heptane and air
  10. customdried

Sources & evidence

ORD record
ord-0054e2e1045a47d5bf47ff40034835b9
Source dataset
uspto-grants-2013_11
Patent number
US08592430B2

Reaction notes

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