Dimethylformamide → 3,4-dihydro-8-methyl-7-[2-[4-(7-methyl-1,2-benzisoxazol-3-yl)-1-piperazinyl]ethyl]-2H,6H-pyrimido[2,1-b][1,3]-thiazin-6-one

HRID 2051019Notes

Reaction equation

HRID 2051019 reaction equation
Br.Br[CH2:3][CH2:4][C:5]1[C:14](=[O:15])[N:13]2[C:8]([S:9][CH2:10][CH2:11][CH2:12]2)=[N:7][C:6]=1[CH3:16].[CH3:17][C:18]1[C:26]2[O:25][N:24]=[C:23]([N:27]3[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]3)[C:22]=2[CH:21]=[CH:20][CH:19]=1.C(=O)([O-])[O-].[Na+].[Na+].CN(C)C=O>O>[CH3:16][C:6]1[N:7]=[C:8]2[N:13]([C:14](=[O:15])[C:5]=1[CH2:4][CH2:3][N:30]1[CH2:31][CH2:32][N:27]([C:23]3[C:22]4[CH:21]=[CH:20][CH:19]=[C:18]([CH3:17])[C:26]=4[O:25][N:24]=3)[CH2:28][CH2:29]1)[CH2:12][CH2:11][CH2:10][S:9]2

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 150574497-Methyl-3-(1-piperazinyl)-1,2-benzisoxazoleHCID 155864667-(2-bromoethyl)-3,4-dihydro-8-methyl-2H,6H-pyrimido[2,1-b][1,3]thiazin-6-one monohydrobromide

Product 1

HCID 151705153,4-dihydro-8-methyl-7-[2-[4-(7-methyl-1,2-benzisoxazol-3-yl)-1-piperazinyl]ethyl]-2H,6H-pyrimido[2,1-b][1,3]-thiazin-6-oneYield 44.6%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 7.4 parts of 7-(2-bromoethyl)-3,4-dihydro-8-methyl-2H,6H-pyrimido-[2,1-b][1,3]thiazin-6-one monohydrobromide, 4.4 parts of 7-methyl-3-(1-piperazinyl)-1,2-benzisoxazole, 10 parts of sodium carbonate and 94 parts of N,N-dimethylformamide was stirred overnight at 90° C. After cooling, the reaction mixture was poured into water and the product was extracted with 4-methyl-2-pentanone. The extract was dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (95:5 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from 4-methyl-2-pentanone. The product was filtered off and dried, yielding 3.8 parts (44.6%) of 3,4-dihydro-8-methyl-7-[2-[4-(7-methyl-1,2-benzisoxazol-3-yl)-1-piperazinyl]ethyl]-2H,6H-pyrimido[2,1-b][1,3]-thiazin-6-one; mp. 170.0° C. (compound 2).

Workup

  1. temperatureAfter cooling
  2. extractionthe product was extracted with 4-methyl-2-pentanone
  3. customThe extract was dried
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was purified by column chromatography over silica gel using
  7. additiona mixture of trichloromethane and methanol (95:5 by volume) as eluent
  8. customThe pure fractions were collected
  9. customthe eluent was evaporated
  10. customThe residue was crystallized from 4-methyl-2-pentanone
  11. filtrationThe product was filtered off
  12. customdried

Sources & evidence

ORD record
ord-7d6ba5f0e4b34f0998d196187166d498
Source dataset
uspto-grants-1991_05
Patent number
US05015740

Reaction notes

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