Sodium Carbonate → 6-[2-[4-[[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]amino]-1-piperidinyl]ethyl]-3,7-dimethyl-5H-thiazolo[3,2-a]pyrimidin-5-one

HRID 1493927Notes

Reaction equation

HRID 1493927 reaction equation
Br.Br[CH2:3][CH2:4][C:5]1[C:10](=[O:11])[N:9]2[C:12]([CH3:15])=[CH:13][S:14][C:8]2=[N:7][C:6]=1[CH3:16].Br.Br.[F:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:26][N:27]2[C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=3[N:29]=[C:28]2[NH:36][CH:37]2[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]2)=[CH:22][CH:21]=1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O>[F:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:26][N:27]2[C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=3[N:29]=[C:28]2[NH:36][CH:37]2[CH2:38][CH2:39][N:40]([CH2:3][CH2:4][C:5]3[C:10](=[O:11])[N:9]4[C:12]([CH3:15])=[CH:13][S:14][C:8]4=[N:7][C:6]=3[CH3:16])[CH2:41][CH2:42]2)=[CH:22][CH:21]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 3018631Norastemizole hydrobromideHCID 139830776-(2-Bromoethyl)-3,7-dimethyl-5H-thiazolo[3,2-A]pyrimidin-5-one monohydrobromide

Product 1

HCID 139830786-[2-[4-[[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]amino]-1-piperidinyl]ethyl]-3,7-dimethyl-5H-thiazolo[3,2-a]pyrimidin-5-oneYield 62.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 5.52 parts of 6-(2-bromoethyl)-3,7-dimethyl-5H-thiazolo[3,2-a]pyrimidin-5-one monohydrobromide, 7.3 parts of 1-[(4-fluorophenyl)methyl]-N-(4-piperidinyl)-1H-benzimidazol-2-amine dihydrobromide, 6.4 parts of sodium carbonate and 135 parts of N,N-dimethylformamide was stirred and heated overnight at 70° C. The reaction mixture was poured onto water. The product was extracted with trichloromethane. The extract was dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (94:6 by volume), saturated with ammonia, as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from acetonitrile, yielding 5 parts (62.8%) of 6-[2-[4-[[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]amino]-1-piperidinyl]ethyl]-3,7-dimethyl-5H-thiazolo[3,2-a]pyrimidin-5-one; mp. 141.0° C. (compound 1).

Workup

  1. additionThe reaction mixture was poured onto water
  2. extractionThe product was extracted with trichloromethane
  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 (94:6 by volume)
  8. customThe pure fractions were collected
  9. customthe eluent was evaporated
  10. customThe residue was crystallized from acetonitrile

Sources & evidence

ORD record
ord-263a907e706244c7b1547730c7018c28
Source dataset
uspto-grants-1991_06
Patent number
US05025014

Reaction notes

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