Tetrahydrofuran → cis-4-amino-N-[1-(2-aminoethyl)-3-methoxy-4-piperidinyl]-5-chloro-2,3-dihydro-7-benzofurancarboxamide

HRID 1450226Notes

Reaction equation

HRID 1450226 reaction equation
[NH2:1][C:2]1[C:7]2[CH2:8][CH2:9][O:10][C:6]=2[C:5]([C:11]([NH:13][C@H:14]2[CH2:19][CH2:18][N:17]([CH2:20][C:21]#[N:22])[CH2:16][C@H:15]2[O:23][CH3:24])=[O:12])=[CH:4][C:3]=1[Cl:25].O1CCCC1.[H][H]>[Ni].CO>[NH2:1][C:2]1[C:7]2[CH2:8][CH2:9][O:10][C:6]=2[C:5]([C:11]([NH:13][C@H:14]2[CH2:19][CH2:18][N:17]([CH2:20][CH2:21][NH2:22])[CH2:16][C@H:15]2[O:23][CH3:24])=[O:12])=[CH:4][C:3]=1[Cl:25]

Participants

6

Reactant 3

HCID 8028TetrahydrofuranHCID 86748327cis-4-amino-5-chloro-N-[1-(cyanomethyl)-3-methoxy-4-piperidinyl]-2,3-dihydro-7-benzofurancarboxamideHCID 178418361HCID 178418361, compound

Product 1

HCID 67704537cis-4-amino-N-[1-(2-aminoethyl)-3-methoxy-4-piperidinyl]-5-chloro-2,3-dihydro-7-benzofurancarboxamideYield 53.6%

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 887MethanolSolvent

Procedure

A solution of 15.7 parts of cis-4-amino-5-chloro-N-[1-(cyanomethyl)-3-methoxy4piperidinyl]-2,3-dihydro-7-benzofurancarboxamide in 178 parts of tetrahydrofuran and 158 parts of methanol was hydrogenated at normal pressure and at room temperature with 6 parts of Raney nickel. After the calculated amount of hydrogen was taken up, the catalyst was filtered off and the filtrate was evaporated. The residue was purified by column chromatography (silica gel; CH2Cl2 /CH3OH(NH3) 93:7). The eluent of the desired fraction was evaporated and the residue was crystallized from acetonitrile (to which a few drops of water were added). The product was filtered off at 0° C. and dried in vacuo at 40° C., yielding 8.5 parts (53.6%) of cis-4-amino-N-[1-(2-aminoethyl)-3-methoxy-4-piperidinyl]-5-chloro-2,3-dihydro-7-benzofurancarboxamide (comp. 35).

Workup

  1. filtrationthe catalyst was filtered off
  2. customthe filtrate was evaporated
  3. customThe residue was purified by column chromatography (silica gel; CH2Cl2 /CH3OH(NH3) 93:7)
  4. customThe eluent of the desired fraction was evaporated
  5. customthe residue was crystallized from acetonitrile (to which a few drops of water were added)
  6. filtrationThe product was filtered off at 0° C.
  7. customdried in vacuo at 40° C.

Sources & evidence

ORD record
ord-996b4e8bed3148a1a7308ed5ed96befe
Source dataset
uspto-grants-1997_02
Patent number
US05602129

Reaction notes

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