Triethylamine → 5-[4-{5-(5-Methyl-1,3,4-oxadiazol-2-yl)-1-naphthyl}benzoyl]-1'-methyl-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine]hydrochloride

HRID 1276293Notes

Reaction equation

HRID 1276293 reaction equation
[C:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[C:19]3[C:14](=[C:15]([C:20]4[O:21][C:22]([CH3:25])=[N:23][N:24]=4)[CH:16]=[CH:17][CH:18]=3)[CH:13]=[CH:12][CH:11]=2)=[CH:6][CH:5]=1)([OH:3])=O.[C:26](Cl)(=[O:30])[C:27]([Cl:29])=O.ClCCCC(NC1[N:44]=[C:43](C)[C:42]([C:46]2[CH:55]=[CH:54][C:49](C(OC)=O)=[CH:48][CH:47]=2)=CC=1)=O.[CH2:56]([N:58]([CH2:61]C)[CH2:59][CH3:60])[CH3:57]>ClCCl.CN(C=O)C>[ClH:29].[CH3:25][C:22]1[O:21][C:20]([C:15]2[CH:16]=[CH:17][CH:18]=[C:19]3[C:14]=2[CH:13]=[CH:12][CH:11]=[C:10]3[C:7]2[CH:8]=[CH:9][C:4]([C:1]([N:44]3[C:55]4[CH:54]=[C:49]5[C:27]6([CH2:26][O:30][C:48]5=[CH:47][C:46]=4[CH2:42][CH2:43]3)[CH2:60][CH2:59][N:58]([CH3:61])[CH2:56][CH2:57]6)=[O:3])=[CH:5][CH:6]=2)=[N:24][N:23]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 22115876HCID 22115876, compoundHCID 221158831-(4-Carboxyphenyl)-5-(5-methyl-1,3,4-oxadiazol-2-yl)naphthalene

Product 1

HCID 221158915-[4-{5-(5-Methyl-1,3,4-oxadiazol-2-yl)-1-naphthyl}benzoyl]-1'-methyl-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine]hydrochlorideYield 67%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

1-(4-Carboxyphenyl)-5-(5-methyl-1,3,4-oxadiazol-2-yl)naphthalene (D4) (0.49 g, 0.45 mmol) in dichloromethane was treated with oxalyl chloride (0.047 ml, 0.53 mmol) followed by 1 drop of DMF. This mixture was stirred under Ar for 1 h, washed with potassium carbonate/brine solution, dried (Na2SO4) and evaporated to give a white solid. This was redissolved in dichloromethane (10 ml), and treated with 1'-methyl-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine (D8 in WO 96/19477, 0.100 g, 0.41 mmol) and triethylamine (0.09 ml, 0.65 mmol). The mixture was stirred for 1 h, washed with potassium carbonate/brine solution, dried (Na2SO4) and evaporated. The crude material was purified by chromatography on silica gel, eluting with 0-10% methanol/dichloromethane. This gave the free base of the title compound (0.154 g, 67%) as white solid. This was dissolved in dichloromethane, treated with 1M HCl in ether

Workup

  1. washwashed with potassium carbonate/brine solution
  2. dry with materialdried (Na2SO4)
  3. customevaporated
  4. customto give a white solid
  5. stirringThe mixture was stirred for 1 h
  6. washwashed with potassium carbonate/brine solution
  7. dry with materialdried (Na2SO4)
  8. customevaporated
  9. customThe crude material was purified by chromatography on silica gel
  10. washeluting with 0-10% methanol/dichloromethane

Sources & evidence

ORD record
ord-a630b8ebc6254ece8f38b165eef89216
Source dataset
uspto-grants-2000_12
Patent number
US06166034

Reaction notes

Loading…