Sodium Carbonate → 2-methyl-3-[2-[4-[[9-(2-pyrazinylmethyl)-9H-purin-8-yl]amino]-1-piperidinyl]-ethyl]-4H-pyrido[1,2-a]pyrimidin-4-one

HRID 256662Notes

Reaction equation

HRID 256662 reaction equation
Cl[CH2:2][CH2:3][C:4]1[C:9](=[O:10])[N:8]2[CH:11]=[CH:12][CH:13]=[CH:14][C:7]2=[N:6][C:5]=1[CH3:15].[NH:16]1[CH2:21][CH2:20][CH:19]([NH:22][C:23]2[N:24]([CH2:32][C:33]3[CH:38]=[N:37][CH:36]=[CH:35][N:34]=3)[C:25]3[C:30]([N:31]=2)=[CH:29][N:28]=[CH:27][N:26]=3)[CH2:18][CH2:17]1.C(=O)([O-])[O-].[Na+].[Na+].CN(C)C(=O)C>O>[CH3:15][C:5]1[N:6]=[C:7]2[CH:14]=[CH:13][CH:12]=[CH:11][N:8]2[C:9](=[O:10])[C:4]=1[CH2:3][CH2:2][N:16]1[CH2:17][CH2:18][CH:19]([NH:22][C:23]2[N:24]([CH2:32][C:33]3[CH:38]=[N:37][CH:36]=[CH:35][N:34]=3)[C:25]3[C:30]([N:31]=2)=[CH:29][N:28]=[CH:27][N:26]=3)[CH2:20][CH2:21]1

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 31374DimethylacetamideHCID 8178663-(2-Chloroethyl)-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-oneHCID 19785357N-(4-piperidinyl)-9-(2-pyrazinylmethyl)-9H-purin-8-amine

Product 1

HCID 197853142-methyl-3-[2-[4-[[9-(2-pyrazinylmethyl)-9H-purin-8-yl]amino]-1-piperidinyl]-ethyl]-4H-pyrido[1,2-a]pyrimidin-4-oneYield 31.6%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 1.45 parts of 3-(2-chloroethyl)-2-methyl-4H-pyrido-[1,2-a]pyrimidin-4-one, 2 parts of N-(4-piperidinyl)-9-(2-pyrazinylmethyl)-9H-purin-8-amine, 1 part of sodium carbonate and 45 parts of N,N-dimethylacetamide was stirred and heated overnight at 90° C. The reaction mixture was poured into 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. saturated with ammonia, (95:5 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from acetonitrile. The product was filtered off and dried, yielding 0.9 parts (31.6%) of 2-methyl-3-[2-[4-[[9-(2-pyrazinylmethyl)-9H-purin-8-yl]amino]-1-piperidinyl]-ethyl]-4H-pyrido[1,2-a]pyrimidin-4-one; mp. 180.1° C. (compound 87).

Workup

  1. extractionThe product was extracted with trichloromethane
  2. customThe extract was dried
  3. filtrationfiltered
  4. customevaporated
  5. customThe residue was purified by column chromatography over silica gel using
  6. additiona mixture of trichloromethane and methanol
  7. customThe pure fractions were collected
  8. customthe eluent was evaporated
  9. customThe residue was crystallized from acetonitrile
  10. filtrationThe product was filtered off
  11. customdried

Sources & evidence

ORD record
ord-a5dd4f2a205b453d89f3d8338691c336
Source dataset
uspto-grants-1993_11
Patent number
US05258380

Reaction notes

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