Dimethylformamide → 4-[4-(4-methoxyphenyl)-1-piperazinyl]-N-(3,4,4-trimethyl-2-thiazolidinylidene)-benzenamine

HRID 2106753Notes

Reaction equation

HRID 2106753 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][N:12]([C:15]3[CH:20]=[CH:19][C:18]([NH:21][C:22]4[S:23][CH2:24][C:25]([CH3:28])([CH3:27])[N:26]=4)=[CH:17][CH:16]=3)[CH2:11][CH2:10]2)=[CH:5][CH:4]=1.[H-].[Na+].[CH3:31]N(C)C=O.IC>O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([N:9]2[CH2:10][CH2:11][N:12]([C:15]3[CH:20]=[CH:19][C:18]([N:21]=[C:22]4[N:26]([CH3:31])[C:25]([CH3:28])([CH3:27])[CH2:24][S:23]4)=[CH:17][CH:16]=3)[CH2:13][CH2:14]2)=[CH:7][CH:8]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 151254684,5-dihydro-N-[4-[4-(4-methoxyphenyl)-1-piperazinyl]phenyl]-4,4-dimethyl-2-thiazolamine

Product 1

HCID 230488594-[4-(4-methoxyphenyl)-1-piperazinyl]-N-(3,4,4-trimethyl-2-thiazolidinylidene)-benzenamine

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 37 parts of 4,5-dihydro-N-[4-[4-(4-methoxyphenyl)-1-piperazinyl]phenyl]-4,4-dimethyl-2-thiazolamine, 5 parts of a sodium hydride dispersion 50% and 376 parts of N,N-dimethylformamide was stirred for 2 hours at 70° C. After cooling to room temperature, 14.1 parts of iodomethane were added slowly to the reaction mixture. The whole was stirred for 1 hour at room temperature. The reaction mixture was diluted with water. The precipitated product was filtered off, washed with water and 2-propanol and purified by column chromatography (HPLC) over silica gel using a mixture of dichloromethane and methanol (96:4 by volume) as eluent. The first fraction was collected and the eluent was evaporated. The residue was further purified by column chromatography over silica gel using a mixture of dichloromethane and methanol (98:2 by volume). The pure fractions were collected and the eluent was evaporated. The residue was crystallized from 4-methyl-2-pentanone, yielding 4-[4-(4-methoxyphenyl)-1-piperazinyl]-N-(3,4,4 -trimethyl-2-thiazolidinylidene)-benzenamine (int. 9). The second fraction was collected and boiled in 2-propanol. After cooling, the product was filtered off and dried, yielding 19.5 parts (51.0%) of 4,5-dihydro-N-[4-[4-(4-methoxyphenyl)-1-piperazinyl]phenyl]-N,4,4-trimethyl-2-thiazolamine; mp. 166.6° C. (int. 10)

Workup

  1. temperatureAfter cooling to room temperature
  2. stirringThe whole was stirred for 1 hour at room temperature
  3. filtrationThe precipitated product was filtered off
  4. washwashed with water and 2-propanol
  5. custompurified by column chromatography (HPLC) over silica gel using
  6. additiona mixture of dichloromethane and methanol (96:4 by volume) as eluent
  7. customThe first fraction was collected
  8. customthe eluent was evaporated
  9. customThe residue was further purified by column chromatography over silica gel using
  10. additiona mixture of dichloromethane and methanol (98:2 by volume)
  11. customThe pure fractions were collected
  12. customthe eluent was evaporated
  13. customThe residue was crystallized from 4-methyl-2-pentanone

Sources & evidence

ORD record
ord-34c99b44a8514d6b9c1e4717a8183f5b
Source dataset
uspto-grants-1990_06
Patent number
US04931444

Reaction notes

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