Triethylamine → tert-Butyl 4-{[4-({[(2'-oxospiro[cyclopentane-1,3'-indol]-1'(2'H)-yl)carbonyl]amino}methyl)piperidin-1-yl]methyl}tetrahydro-2H-pyran-4-carboxylate

HRID 733084Notes

Reaction equation

HRID 733084 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]2([CH2:13][CH2:12][CH2:11][CH2:10]2)[C:2]1=[O:14].C(N(CC)CC)C.[C:22]([O:26][C:27]([C:29]1([CH2:35][N:36]2[CH2:41][CH2:40][CH:39]([CH2:42][NH2:43])[CH2:38][CH2:37]2)[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1)=[O:28])([CH3:25])([CH3:24])[CH3:23].[C:44]([O-])(O)=[O:45].[Na+]>C(Cl)Cl>[O:14]=[C:2]1[C:3]2([CH2:13][CH2:12][CH2:11][CH2:10]2)[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[N:1]1[C:44]([NH:43][CH2:42][CH:39]1[CH2:40][CH2:41][N:36]([CH2:35][C:29]2([C:27]([O:26][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:28])[CH2:34][CH2:33][O:32][CH2:31][CH2:30]2)[CH2:37][CH2:38]1)=[O:45]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 3633431',2'-Dihydrospiro[cyclopentane-1,3'-indole]-2'-oneHCID 516892Sodium BicarbonateHCID 67232551tert-Butyl4-{[4-(aminomethyl)piperidin-1-yl]methyl}tetrahydro-2H-pyran-4-carboxylate

Product 1

HCID 68472179tert-Butyl 4-{[4-({[(2'-oxospiro[cyclopentane-1,3'-indol]-1'(2'H)-yl)carbonyl]amino}methyl)piperidin-1-yl]methyl}tetrahydro-2H-pyran-4-carboxylateYield 75%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of spiro[cyclopentane-1,3′-indol]-2′(1′H)-one (600 mg, 3.2 mmol, Howard, Harry R. et al., J. Med. Chem., 1996, 39, 143) and triethylamine (972 mg, 9.6 mmol) in CH2Cl2 (20 mL) was added 4-nitrochloroformate (677 mg, 3.4 mmol) at room temperature, and stirred at ambient temperature for 3 h. Then, a solution of tert-butyl 4-{[4-(aminomethyl)piperidin-1-yl]methyl}tetrahydro-2H-pyran-4-carboxylate (1.0 g, 3.2 mmol, step 5 of Example 1) in CH2Cl2 (5 mL) was added at room temperature, and stirred for 18 h. Then, sat. NaHCO3 aq. (20 mL) was added, extracted with CH2Cl2 (30 mL×3), dried over MgSO4, filtered and concentrated gave yellow brown oil. The residue was chromatographed on a column of aminopropyl-silica gel eluting with hexane/ethyl acetate (11:1) to give 1.3 g (75%) of the title compound as clear yellow oil.

Workup

  1. stirringstirred for 18 h
  2. extractionextracted with CH2Cl2 (30 mL×3)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customgave yellow brown oil
  7. customThe residue was chromatographed on a column of aminopropyl-silica gel eluting with hexane/ethyl acetate (11:1)

Sources & evidence

ORD record
ord-f021ab92bb68495cbc428a4007756d6b
Source dataset
uspto-grants-2009_09
Patent number
US07589109B2

Reaction notes

Loading…