Triethylamine → SB-236057

HRID 1741109Notes

Reaction equation

HRID 1741109 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([C:8]2[O:9][C:10]([CH3:13])=[N:11][N:12]=2)[CH:5]=[CH:4][C:3]=1[C:14]1[CH:19]=[CH:18][C:17]([C:20]([OH:22])=O)=[CH:16][CH:15]=1.[CH2:23]([N:25]1[CH2:30][CH2:29][C:28]2([C:41]3[C:33](=[CH:34][C:35]4[CH2:36][CH2:37][NH:38][C:39]=4[CH:40]=3)[O:32][CH2:31]2)[CH2:27][CH2:26]1)[CH3:24].C(N(CC)CC)C>S(Cl)(Cl)=O.C1COCC1>[CH2:23]([N:25]1[CH2:30][CH2:29][C:28]2([C:41]3[C:33](=[CH:34][C:35]4[CH2:36][CH2:37][N:38]([C:20]([C:17]5[CH:16]=[CH:15][C:14]([C:3]6[CH:4]=[CH:5][C:6]([C:8]7[O:9][C:10]([CH3:13])=[N:11][N:12]=7)=[CH:7][C:2]=6[CH3:1])=[CH:19][CH:18]=5)=[O:22])[C:39]=4[CH:40]=3)[O:32][CH2:31]2)[CH2:27][CH2:26]1)[CH3:24]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 186900662'-Methyl-4'-(5-methyl-1,3,4-oxadiazol-2-yl)biphenyl-4-carboxylic acidHCID 218337441'-Ethyl-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine]

Product 1

HCID 5311426SB-236057Yield 68%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 24386Thionyl ChlorideSolvent

Conditions

Temperature
45 °C

Procedure

A stirred suspension of 2'-methyl-4'-(5-methyl-1,3,4-oxadiazol-2-yl)biphenyl-4-carboxylic acid (D11, 0.53 g, 1.8 mmole) in thionyl chloride (8 ml) was heated at about 45° C. for 30 minutes, then concentrated in vacuo. The yellow solid was dissolved in THF (10 ml)/dichloromethane (5 ml) and added to a stirred solution of 1'-ethyl-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine] (D109, 0.46 g, 1.8 mmole) and triethylamine (0.50 ml, 3.6 mmole) in THF (15 ml) at 5° C. under argon. The solution was stirred at room temp. for 2 h, then concentrated in vacuo. The residue was treated with 10% Na2CO3 solution and extracted with ethyl acetate. The extract was dried (Na2SO4), concentrated in vacuo and the residue chromatographed on silica gel eluting with 3% methanol/chloroform and the yellow oil obtained passed through a short basic alumina column eluting with ethyl acetate to afford the title compound as a beige foam (0.62 g, 68%). This was converted to its hydrochloride (mp 269-273° C.) and mesylate (mp 275-279° C.) salts.

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe yellow solid was dissolved in THF (10 ml)/dichloromethane (5 ml)
  3. concentrationconcentrated in vacuo
  4. additionThe residue was treated with 10% Na2CO3 solution
  5. extractionextracted with ethyl acetate
  6. dry with materialThe extract was dried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customthe residue chromatographed on silica gel eluting with 3% methanol/chloroform
  9. customthe yellow oil obtained
  10. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-a122607a60b54c1581c7a8b3ef571d68
Source dataset
uspto-grants-1999_10
Patent number
US05972951

Reaction notes

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