Hydrochloric Acid → HCID 19045313, compound

HRID 1591228Notes

Reaction equation

HRID 1591228 reaction equation
[CH:1](OCC)(OCC)OCC.[NH2:11][C:12]1[C:13]([NH2:38])=[CH:14][C:15]2[O:35][C:19]3([CH2:24][CH2:23][N:22]([CH2:25][CH2:26][C:27]4[CH:32]=[CH:31][C:30]([C:33]#[N:34])=[CH:29][CH:28]=4)[CH2:21][CH2:20]3)[CH2:18][C:17](=[O:36])[C:16]=2[CH:37]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.[ClH:50].C(=O)([O-])O.[Na+]>C(OCC)(=O)C.C(O)C>[ClH:50].[ClH:50].[C:33]([C:30]1[CH:31]=[CH:32][C:27]([CH2:26][CH2:25][N:22]2[CH2:23][CH2:24][C:19]3([O:35][C:15]4=[CH:14][C:13]5[N:38]=[CH:1][NH:11][C:12]=5[CH:37]=[C:16]4[C:17](=[O:36])[CH2:18]3)[CH2:20][CH2:21]2)=[CH:28][CH:29]=1)#[N:34]

Participants

8

Reactant 5

HCID 313Hydrochloric Acid2×HCID 6101p-Toluenesulfonic acidHCID 31214Ethyl orthoformate2×HCID 516892Sodium BicarbonateHCID 19045426HCID 19045426, compound

Product 1

HCID 19045313HCID 19045313, compoundYield 55%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

Triethyl orthoformate (75 ml, 67 mg, 0.45 mmol) was added to a stirred suspension of 6,7-diamino-3,4-dihydro-1'-[2-(4-cyanophenyl)ethyl]spiro[(2H)-1-benzopyran-2,4'-piperidine]-4-one (56 mg, 0.15 mmol) and p-toluensulfonic acid (monohydrate, 10 mg) in ethyl acetate (5 ml). The mixture was heated under reflux for 1 hour, further triethyl orthoformate (75 ml) was added and the mixture was heated under reflux for 1.5 hour. The mixture was cooled and aqueous HCl (1N, 5 ml) was added. The mixture was stirred for 15 minutes, poured into aqueous sodium hydrogen carbonate (saturated, 25 ml) and extracted with dichloromethane (3×25 ml). The combined organic fractions were dried (Na2SO4) and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with CH2Cl2 /MeOH/NH3 (Aq.) (95:5:0.5) to give a yellow solid which was suspended in ethanol (1 ml) and treated with ethanolic HCl (6M, 0.2 ml). The mixture was stirred for 1 hour, cooled and the precipitate was collected and dried in vacuo to give the title compound as a tan solid (40 mg, 55%), m.p >250° C.

Workup

  1. temperatureThe mixture was heated
  2. temperatureunder reflux for 1 hour
  3. temperaturethe mixture was heated
  4. temperatureunder reflux for 1.5 hour
  5. temperatureThe mixture was cooled
  6. extractionextracted with dichloromethane (3×25 ml)
  7. dry with materialThe combined organic fractions were dried (Na2SO4)
  8. customevaporated under reduced pressure
  9. customThe residue was purified by column chromatography on silica gel
  10. washeluting with CH2Cl2 /MeOH/NH3 (Aq.) (95:5:0.5)
  11. customto give a yellow solid which
  12. stirringThe mixture was stirred for 1 hour
  13. temperaturecooled
  14. customthe precipitate was collected
  15. customdried in vacuo

Sources & evidence

ORD record
ord-d68bd6520e004c5d9634b1b7d3356fdd
Source dataset
uspto-grants-1993_04
Patent number
US05206240

Reaction notes

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