Chloroform → cis-4-amino-5-chloro-2,3-dihydro-N-[3-methoxy-1-[2-[methyl(1-pyrrolidinylcarbonyl)amino]ethyl]-4-piperidinyl]-7-benzofurancarboxamide monohydrate

HRID 742108Notes

Reaction equation

HRID 742108 reaction equation
O.[NH2:2][C:3]1[C:8]2[CH2:9][CH2:10][O:11][C:7]=2[C:6]([C:12]([NH:14][C@H:15]2[CH2:20][CH2:19][N:18]([CH2:21][CH2:22][NH:23][CH3:24])[CH2:17][C@H:16]2[O:25][CH3:26])=[O:13])=[CH:5][C:4]=1[Cl:27].ClC(Cl)Cl.[N:32]1([C:37](Cl)=[O:38])[CH2:36][CH2:35][CH2:34][CH2:33]1>C(N(CC)CC)C>[OH2:11].[NH2:2][C:3]1[C:8]2[CH2:9][CH2:10][O:11][C:7]=2[C:6]([C:12]([NH:14][C@H:15]2[CH2:20][CH2:19][N:18]([CH2:21][CH2:22][N:23]([CH3:24])[C:37]([N:32]3[CH2:36][CH2:35][CH2:34][CH2:33]3)=[O:38])[CH2:17][C@H:16]2[O:25][CH3:26])=[O:13])=[CH:5][C:4]=1[Cl:27]

Participants

5

Reactant 3

HCID 6212ChloroformHCID 709371-Pyrrolidinecarbonyl chlorideHCID 67704506cis-4-amino-5-chloro-2,3-dihydro-N-[3-methoxy-1-[2-(methylamino)ethyl]-4-piperidinyl]-7-benzofurancarboxamide monohydrate

Product 1

HCID 67704495cis-4-amino-5-chloro-2,3-dihydro-N-[3-methoxy-1-[2-[methyl(1-pyrrolidinylcarbonyl)amino]ethyl]-4-piperidinyl]-7-benzofurancarboxamide monohydrateYield 73.6%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Conditions

Temperature
0 °C

Procedure

To a cooled (ice-bath) mixture of 3.8 parts of cis-4-amino-5-chloro-2,3-dihydro-N-[3-methoxy-1-[2-(methylamino)ethyl]-4-piperidinyl]-7-benzofurancarboxamide monohydrate in 104.3 parts of trichloromethane were added 1.3 parts of 1-pyrrolidinecarbonyl chloride. After stirring for 15 min. at 0° C., there were added dropwise 1.31 parts of N,N-diethylethanamine, keeping the temperature below 10° C. Stirring was continued for 20 hours at room temperature. The reaction mixture was washed with water, dried, filtered and evaporated. The residue was crystallized from acetonitrile (to which some water was added). The product was filtered off at 0° C. and dried in vacuo at 40° C., yielding 3.3 parts (73.6%) of cis-4-amino-5-chloro-2,3-dihydro-N-[3-methoxy-1-[2[methyl(1-pyrrolidinylcarbonyl)amino]ethyl]-4-piperdinyl]-7-benzofurancarboxamide monohydrate; mp. 112.0° C. (comp. 43).

Workup

  1. temperatureTo a cooled
  2. customthe temperature below 10° C
  3. stirringStirring
  4. waitwas continued for 20 hours at room temperature
  5. washThe reaction mixture was washed with water
  6. customdried
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was crystallized from acetonitrile (to which some water
  10. additionwas added)
  11. filtrationThe product was filtered off at 0° C.
  12. customdried in vacuo at 40° C.

Sources & evidence

ORD record
ord-7f118e4d36dc4fb3a4cec0e9a379496c
Source dataset
uspto-grants-1996_09
Patent number
US05552553

Reaction notes

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