Sodium Carbonate → 9-[(4-fluorophenyl)methyl]-N-[1-[2-(2-thiazolylamino)ethyl)-4-piperidinyl]-9H-purin-8-amine

HRID 256672Notes

Reaction equation

HRID 256672 reaction equation
Br[C:2]1[S:3][CH:4]=[CH:5][N:6]=1.[NH2:7][CH2:8][CH2:9][N:10]1[CH2:15][CH2:14][CH:13]([NH:16][C:17]2[N:18]([CH2:26][C:27]3[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=3)[C:19]3[C:24]([N:25]=2)=[CH:23][N:22]=[CH:21][N:20]=3)[CH2:12][CH2:11]1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C(=O)C>[F:33][C:30]1[CH:29]=[CH:28][C:27]([CH2:26][N:18]2[C:17]([NH:16][CH:13]3[CH2:14][CH2:15][N:10]([CH2:9][CH2:8][NH:7][C:2]4[S:3][CH:4]=[CH:5][N:6]=4)[CH2:11][CH2:12]3)=[N:25][C:24]3[C:19]2=[N:20][CH:21]=[N:22][CH:23]=3)=[CH:32][CH:31]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 764302-BromothiazoleHCID 19785318N-[1-(2-aminoethyl)-4-piperidinyl]-9-[(4-fluorophenyl)methyl]-9H-purin-8-amine

Product 1

HCID 197853019-[(4-fluorophenyl)methyl]-N-[1-[2-(2-thiazolylamino)ethyl)-4-piperidinyl]-9H-purin-8-amineYield 26.5%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 3.3 parts of 2-bromothiazole, 5.55 parts of N-[1-(2-aminoethyl)-4-piperidinyl]-9-[(4-fluorophenyl)methyl]-9H-purin-8-amine, 2.12 parts of sodium carbonate and 18 parts of N,N-dimethylacetamide was stirred and heated for 20 hours at 130° C. After cooling, the reaction mixture was poured onto 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, methanol and methanol saturated with ammonia, (90:5:5 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 in high vacuo at 100° C., yielding 1.8 parts (26.5%) of 9-[(4-fluorophenyl)methyl]-N-[1-[2-(2-thiazolylamino)ethyl)-4-piperidinyl]-9H-purin-8-amine; mp. 165.4° C. (compound 172).

Workup

  1. temperatureAfter cooling
  2. additionthe reaction mixture was poured onto water
  3. extractionthe product was extracted with 4-methyl-2-pentanone
  4. customThe extract was dried
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by column chromatography over silica gel using
  8. additiona mixture of trichloromethane, methanol and methanol saturated with ammonia, (90:5:5 by volume) as eluent
  9. customThe pure fractions were collected
  10. customthe eluent was evaporated
  11. customThe residue was crystallized from acetonitrile
  12. filtrationThe product was filtered off
  13. customdried in high vacuo at 100° C.

Sources & evidence

ORD record
ord-206999dec95643568771f08e87551483
Source dataset
uspto-grants-1993_11
Patent number
US05258380

Reaction notes

Loading…