Ammonia → HCID 15586438, compound

HRID 371107Notes

Reaction equation

HRID 371107 reaction equation
[F:1][C:2]1[CH:29]=[CH:28][C:5]([C:6]([CH:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][C:16]3[C:21](=[O:22])[N:20]4[C:23]([CH3:26])=[CH:24][S:25][C:19]4=[N:18][C:17]=3[CH3:27])[CH2:10][CH2:9]2)=[O:7])=[CH:4][CH:3]=1.C(OCC)(OCC)[O:31][CH2:32][CH3:33].[CH3:40][C:41]1C=CC(S(O)(=O)=O)=CC=1.N>C(O)C>[CH2:40]([O:7][C:6]([O:31][CH2:32][CH3:33])([C:5]1[CH:4]=[CH:3][C:2]([F:1])=[CH:29][CH:28]=1)[CH:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][C:16]2[C:21](=[O:22])[N:20]3[C:23]([CH3:26])=[CH:24][S:25][C:19]3=[N:18][C:17]=2[CH3:27])[CH2:10][CH2:9]1)[CH3:41]

Participants

6

Reactant 4

HCID 222AmmoniaHCID 6101p-Toluenesulfonic acidHCID 31214Ethyl orthoformateHCID 15586425HCID 15586425, compound

Product 1

HCID 15586438HCID 15586438, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 8.3 parts of 6-[2-[4-(4-fluorobenzoyl)-1-piperidinyl]ethyl]-3,7-dimethyl-5H-thiazolo[3,2-a]pyrimidin-5-one, 10 parts of 1,1',1"-[methylidynetris(oxy)]trisethane, 4 parts of 4-methylbenzenesulfonic acid and 80 parts of ethanol was stirred and refluxed for 72 hours. After cooling, gaseous ammonia was introduced. The formed precipitate was filtered off and the filtrate was evaporated. The residue was purified by column-chromatography over silica gel using a mixture of trichloromethane and ethanol (90:10 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was further purified by reversed phase chromatography over LiChroprep. RP 18 using a mixture of water (containing 0.5% ammonium acetate) and methanol (containing 0.1% of N-(1-methylethyl)-2-propanamine) (15:85 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from 2,2'-oxybispropane, yielding 0.6 parts of 6-[2-[4 -[diethoxy(4-fluorophenyl)methyl]-1-piperidinyl]ethyl]-3,7-dimethyl-5H-thiazolo[3,2-a]pyrimidin-5-one; mp. 115.6° C. (compound 36).

Workup

  1. temperaturerefluxed for 72 hours
  2. temperatureAfter cooling
  3. filtrationThe formed precipitate was filtered off
  4. customthe filtrate was evaporated
  5. customThe residue was purified by column-chromatography over silica gel using
  6. additiona mixture of trichloromethane and ethanol (90:10 by volume) as eluent
  7. customThe pure fractions were collected
  8. customthe eluent was evaporated
  9. customThe residue was further purified by reversed phase chromatography over LiChroprep
  10. additionRP 18 using a mixture of water (containing 0.5% ammonium acetate) and methanol (containing 0.1% of N-(1-methylethyl)-2-propanamine) (15:85 by volume) as eluent
  11. customThe pure fractions were collected
  12. customthe eluent was evaporated
  13. customThe residue was crystallized from 2,2'-oxybispropane

Sources & evidence

ORD record
ord-102f7352f5eb4241a8ce96c12ddfdb55
Source dataset
uspto-grants-1985_07
Patent number
US04529727

Reaction notes

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