Water → HCID 86741816, compound

HRID 2309636Notes

Reaction equation

HRID 2309636 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 Iodide2×HCID 10340Sodium Carbonate2×HCID 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 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 eluant. 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-3988e34d4f574023b7af2a6ae9a961d4
Source dataset
uspto-grants-1987_09
Patent number
US04695575

Reaction notes

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