Water → 2-amino-N-[2-[4-[[9-[(4-fluorophenyl)methyl]-9H-purin-8-yl]amino]-1-piperidinyl]ethyl]benzamide (E)-2-butenedioate

HRID 2248826Notes

Reaction equation

HRID 2248826 reaction equation
[NH:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[C:4](=[O:11])[O:3]C1=O.[NH2:13][CH2:14][CH2:15][N:16]1[CH2:21][CH2:20][CH:19]([NH:22][C:23]2[N:24]([CH2:32][C:33]3[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=3)[C:25]3[C:30]([N:31]=2)=[CH:29][N:28]=[CH:27][N:26]=3)[CH2:18][CH2:17]1.CN(C)[CH:42]=[O:43].[OH2:45]>>[C:42]([OH:43])(=[O:45])/[CH:6]=[CH:5]/[C:4]([OH:11])=[O:3].[NH2:1][C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=1[C:4]([NH:13][CH2:14][CH2:15][N:16]1[CH2:17][CH2:18][CH:19]([NH:22][C:23]2[N:24]([CH2:32][C:33]3[CH:34]=[CH:35][C:36]([F:39])=[CH:37][CH:38]=3)[C:25]3[C:30]([N:31]=2)=[CH:29][N:28]=[CH:27][N:26]=3)[CH2:20][CH2:21]1)=[O:11]

Participants

5

Reactant 4

HCID 962WaterHCID 6228DimethylformamideHCID 8359Isatoic AnhydrideHCID 19785318N-[1-(2-aminoethyl)-4-piperidinyl]-9-[(4-fluorophenyl)methyl]-9H-purin-8-amine

Product 1

HCID 1317169772-amino-N-[2-[4-[[9-[(4-fluorophenyl)methyl]-9H-purin-8-yl]amino]-1-piperidinyl]ethyl]benzamide (E)-2-butenedioateYield 50%

Conditions

Temperature
70 °C

Procedure

A mixture of 1.4 parts of 2H-3,1-benzoxazine-2,4-(1H)-dione, 3.7 parts of N-[1-(2-aminoethyl)-4-piperidinyl]-9-[(4-fluorophenyl)methyl]-9H-purin-8-amine and 45 parts of N,N-dimethylformamide was stirred for 4 hours at 70° C. After cooling, the reaction mixture was poured into water and the product was extracted with 4-methyl-2-pentanone. The extract was washed with water, 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 (E)-2-butenedioate salt in ethanol. The salt was filtered off and dried, yielding 4.3 parts (50%) of 2-amino-N-[2-[4-[[9-[(4-fluorophenyl)methyl]-9H-purin-8-yl]amino]-1-piperidinyl]ethyl]benzamide (E)-2-butenedioate(2:5): mp. 164° C. (compound 178).

Workup

  1. temperatureAfter cooling
  2. extractionthe product was extracted with 4-methyl-2-pentanone
  3. washThe extract was washed with water
  4. customdried
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by column chromatography over silica gel using
  8. additiona mixture of trichloromethane and methanol
  9. customThe pure fractions were collected
  10. customthe eluent was evaporated
  11. filtrationThe salt was filtered off
  12. customdried

Sources & evidence

ORD record
ord-f39c16e6fa8c4c62b3c4ef14b34437fb
Source dataset
uspto-grants-1991_08
Patent number
US05041448

Reaction notes

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