Acetic Acid → p-[N-((6RS)-2-Methyl-4-oxo-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl)-N-(prop-2-ynyl)amino]benzoic acid

HRID 1289230Notes

Reaction equation

HRID 1289230 reaction equation
[CH3:1][C:2]1[NH:11][C:10](=[O:12])[C:9]2[C:4](=[CH:5][C:6]3[CH2:15][CH2:14][CH:13]([N:16]([C:20]4[CH:37]=[CH:36][C:23](C(N[C@H](C(O)=O)CCC(O)=O)=O)=[CH:22][CH:21]=4)[CH2:17][C:18]#[CH:19])[C:7]=3[CH:8]=2)[N:3]=1.NC(CO)(CO)CO.[C:46]([OH:49])(=[O:48])C>[Cl-].[Zn+2].[Cl-]>[CH3:1][C:2]1[NH:11][C:10](=[O:12])[C:9]2[C:4](=[CH:5][C:6]3[CH2:15][CH2:14][CH:13]([N:16]([C:20]4[CH:37]=[CH:36][C:23]([C:46]([OH:49])=[O:48])=[CH:22][CH:21]=4)[CH2:17][C:18]#[CH:19])[C:7]=3[CH:8]=2)[N:3]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 6503Tris(hydroxymethyl)aminomethaneHCID 135462847HCID 135462847, compound

Product 1

HCID 135443466p-[N-((6RS)-2-Methyl-4-oxo-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl)-N-(prop-2-ynyl)amino]benzoic acid

Reagents, catalysts & solvents 1

HCID 3007855ZincchlorideCatalyst

Conditions

Temperature
37 °C

Procedure

A mixture of N-{p-[N-((6RS)-2-methyl-4-oxo-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl)-N-(prop-2-ynyl)amino]benzoyl}-L-glutamic acid (6 g), carboxypeptidase G2 (2000 units) and tris buffer [prepared by mixing 2-amino-2-hydroxymethyl-1,3-propanediol (12.11 g), zinc chloride (0.035 g) and distilled water (950 ml), by adjusting the basicity of the mixture to pH 7.3 by the addition of 2N aqueous hydrochloric acid and by adding sufficient distilled water to give a final volume of 1 L; 750 ml] was stirred and heated to 37° C. for 30 hours. A second portion of carboxypeptidase G2 (2000 units) was added and the mixture was heated to 37° C. for a further 24 hours. The mixture was cooled to 0° C. and acidified to pH 4 by the addition of glacial acetic acid. The precipitate was isolated, washed with water and dried under vacuum. There was thus obtained p-[N-((6RS)-2-methyl-4-oxo-3,4,7,8-tetrahydro-6H-cyclopenta[a]quinazolin-6-yl)-N-(prop-2-ynyl)amino]benzoic acid as a solid (4 g), m.p. 264° C.;

Workup

  1. customprepared
  2. distillationdistilled water (950 ml)
  3. additionby the addition of 2N aqueous hydrochloric acid
  4. additionby adding sufficient
  5. distillationdistilled water
  6. customto give a final volume of 1 L
  7. additionA second portion of carboxypeptidase G2 (2000 units) was added
  8. temperaturethe mixture was heated to 37° C. for a further 24 hours
  9. temperatureThe mixture was cooled to 0° C.
  10. customThe precipitate was isolated
  11. washwashed with water
  12. customdried under vacuum

Sources & evidence

ORD record
ord-4d28c93b7a054fc89a95ef4020234344
Source dataset
uspto-grants-1998_05
Patent number
US05747499

Reaction notes

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