Water → HCID 86741816, compound

HRID 1904840Notes

Reaction equation

HRID 1904840 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].[F:17][C:18]1[CH:23]=[CH:22][C:21]([CH2:24][N:25]2[C:29]3=[N:30][CH:31]=[CH:32][CH:33]=[C:28]3[N:27]=[C:26]2[CH2:34][CH:35]2[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]2)=[CH:20][CH:19]=1.[C:41](=[O:44])([O-:43])[O-].[Na+].[Na+].[I-].[K+].[OH2:49]>CN(C)C=O>[C:14]([OH:15])(=[O:49])[C:41]([OH:43])=[O:44].[F:17][C:18]1[CH:19]=[CH:20][C:21]([CH2:24][N:25]2[C:29]3=[N:30][CH:31]=[CH:32][CH:33]=[C:28]3[N:27]=[C:26]2[CH2:34][CH:35]2[CH2:40][CH2:39][N:38]([CH2:3][CH2:4][C:5]3[C:14](=[O:15])[N:13]4[C:8]([S:9][CH2:10][CH2:11][CH2:12]4)=[N:7][C:6]=3[CH3:16])[CH2:37][CH2:36]2)=[CH:22][CH:23]=1

Participants

7

Reactant 5

HCID 962WaterHCID 4875Potassium IodideHCID 10340Sodium CarbonateHCID 14013372HCID 14013372, compoundHCID 155864667-(2-bromoethyl)-3,4-dihydro-8-methyl-2H,6H-pyrimido[2,1-b][1,3]thiazin-6-one monohydrobromide

Product 1

HCID 86741816HCID 86741816, compoundYield 61%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 3.14 parts of 7-(2-bromoethyl)-3,4-dihydro-8-methyl-2H,6H-pyrimido[2,1-b][1,3]thiazin-6-one monohydrobromide, 3.5 parts of 3-[(4-fluorophenyl)methyl]-2-(4-piperidinylmethyl)-3H-imidazo-[4,5-b]pyridin, 4 parts of sodium carbonate, 0.1 parts of potassium iodide and 90 parts of N,N-dimethylformamide was stirred and heated overnight at 70° C. After cooling, water was added. 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, saturated with ammonia, (95:5 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was converted into the ethanedioate salt in ethanol. The salt was filtered off and dried, yielding 3.7 parts (61%) of 7-[2-[4-[[3-[(4-fluorophenyl)methyl]-3H-imidazo[4,5-b]pyridin-2-yl]methyl]-1 -piperidinyl]ethyl]-3,4-dihydro-8-methyl-2H,6H-pyrimido[2,1-b][1,3]thiazin-6-one ethanedioate (1:2); mp. 190.5° C. (205).

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
  8. customThe pure fractions were collected
  9. customthe eluent was evaporated
  10. filtrationThe salt was filtered off
  11. customdried

Sources & evidence

ORD record
ord-163e2befe8874ce7b6080a93fcd82fe2
Source dataset
uspto-grants-1989_06
Patent number
US04839374

Reaction notes

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