Triethylamine → cis-4-amino-5-chloro-2-methoxy-N-[3-methoxy-1-[2-(2-pyrimidinylamino)ethyl]-4-piperidinyl]benzamide monohydrate

HRID 1165053Notes

Reaction equation

HRID 1165053 reaction equation
[NH2:1][C:2]1[C:21]([Cl:22])=[CH:20][C:5]([C:6]([NH:8][C@H:9]2[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][NH2:17])[CH2:11][C@H:10]2[O:18][CH3:19])=[O:7])=[C:4]([O:23][CH3:24])[CH:3]=1.C(N(CC)CC)C.Cl[C:33]1[N:38]=[CH:37][CH:36]=[CH:35][N:34]=1.C(=O)([O-])[O-].[Na+].[Na+]>ClC(Cl)Cl>[OH2:7].[NH2:1][C:2]1[C:21]([Cl:22])=[CH:20][C:5]([C:6]([NH:8][C@H:9]2[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][NH:17][C:33]3[N:38]=[CH:37][CH:36]=[CH:35][N:34]=3)[CH2:11][C@H:10]2[O:18][CH3:19])=[O:7])=[C:4]([O:23][CH3:24])[CH:3]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 10340Sodium CarbonateHCID 744042-ChloropyrimidineHCID 14854954cis-4-amino-N-[1-(2-aminoethyl)-3-methoxy-4-piperidinyl]-5-chloro-2-methoxybenzamide

Product 1

HCID 67915675cis-4-amino-5-chloro-2-methoxy-N-[3-methoxy-1-[2-(2-pyrimidinylamino)ethyl]-4-piperidinyl]benzamide monohydrateYield 29.2%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent2×

Procedure

To a stirred mixture of 4.28 parts of cis-4-amino-N-[1-(2-aminoethyl)-3-methoxy-4-piperidinyl]-5-chloro-2-methoxybenzamide, 1.21 parts of N,N-diethylethanamine and 150 parts of trichloromethane was added a solution of 1.5 parts of 2-chloropyrimidine in 75 parts of trichloromethane. The whole was stirred and refluxed for 80 hours. After cooling, the reaction mixture was poured into a saturated sodium carbonate solution. The product was extracted with trichloromethane. 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 (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 1.52 parts (29.2%) of cis-4-amino-5-chloro-2-methoxy-N-[3-methoxy-1-[2-(2-pyrimidinylamino)ethyl]-4-piperidinyl]benzamide monohydrate; mp. 123.5° C. (compound 46).

Workup

  1. temperaturerefluxed for 80 hours
  2. temperatureAfter cooling
  3. extractionThe product was extracted with trichloromethane
  4. washThe extract was washed with water
  5. customdried
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by column chromatography over silica gel using
  9. additiona mixture of trichloromethane and methanol (95:5 by volume) as eluent
  10. customThe pure fractions were collected
  11. customthe eluent was evaporated
  12. customThe residue was crystallized from acetonitrile
  13. filtrationThe product was filtered off
  14. customdried

Sources & evidence

ORD record
ord-6e267d91baeb4c68ace167df96e6b0c3
Source dataset
uspto-grants-1990_03
Patent number
US04906643

Reaction notes

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