Triethylamine → 3,5-Dimethyl-isoxazole-4-sulfonic Acid 7-{[1-(piperidine-4-carbonyl)-piperidin-4-ylmethyl]-propyl-amino}-5,6,7,8-tetrahydro-naphthalen-2-yl Ester

HRID 983489Notes

Reaction equation

HRID 983489 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([CH2:7][N:8]([CH2:30][CH2:31][CH3:32])[CH:9]2[CH2:18][C:17]3[CH:16]=[C:15]([O:19][S:20]([C:23]4[C:24]([CH3:29])=[N:25][O:26][C:27]=4[CH3:28])(=[O:22])=[O:21])[CH:14]=[CH:13][C:12]=3[CH2:11][CH2:10]2)[CH2:3][CH2:2]1.C(OC([N:40]1[CH2:45][CH2:44][CH:43]([C:46](O)=[O:47])[CH2:42][CH2:41]1)=O)(C)(C)C.CCN=C=NCCCN(C)C.C(N(CC)CC)C>ClCCl>[NH:40]1[CH2:45][CH2:44][CH:43]([C:46]([N:1]2[CH2:6][CH2:5][CH:4]([CH2:7][N:8]([CH2:30][CH2:31][CH3:32])[CH:9]3[CH2:18][C:17]4[CH:16]=[C:15]([O:19][S:20]([C:23]5[C:24]([CH3:29])=[N:25][O:26][C:27]=5[CH3:28])(=[O:22])=[O:21])[CH:14]=[CH:13][C:12]=4[CH2:11][CH2:10]3)[CH2:3][CH2:2]2)=[O:47])[CH2:42][CH2:41]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acidHCID 213627933,5-Dimethyl-isoxazole-4-sulfonic acid 7-(piperidin-4-ylmethyl-propyl-amino)-5,6,7,8-tetrahydro-naphthalen-2-yl ester

Product 1

HCID 102185313,5-Dimethyl-isoxazole-4-sulfonic Acid 7-{[1-(piperidine-4-carbonyl)-piperidin-4-ylmethyl]-propyl-amino}-5,6,7,8-tetrahydro-naphthalen-2-yl EsterYield 89.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Under an inert atmosphere 3,5-dimethyl-isoxazole-4-sulfonic acid 7-(piperidin-4-ylmethyl-propyl-amino)-5,6,7,8-tetrahydro-naphthalen-2-yl ester (400 mg, 0.87 mmol), piperidine-1,4-dicarboxylic acid mono-tert-butyl ester (199 mg, 0.87 mmol, 1 eq.), EDCI (166 mg, 0.87 mmol, 1 eq.), triethylamine (0.25 mL, 1.79 mmol, 2 eq.), and dichloromethane (35 mL) were combined. The mixture was stirred at room temperature for 48 h and then concentrated in vacuo. The residue was taken up in EtOAc (50 mL) and washed with water (30 mL), 1N NaOH (30 mL), brine (30 mL), and then dried (MgSO4). The solution was filtered and concentrated to afford a yellow oil. The oil was flash chromatographed on silica gel eluting with 20% acetone in hexanes to afford the protected amine as a foam (447 mg), which was deprotected with trifluoroacetic acid, as described herein, to afford 3,5-dimethyl-isoxazole-4-sulfonic acid 7-{[1-(piperidine-4-carbonyl)-piperidin-4-ylmethyl]-propyl-amino}-5,6,7,8-tetrahydro-naphthalen-2-yl ester (320 mg), 114M+H]+=609.

Workup

  1. concentrationconcentrated in vacuo
  2. washwashed with water (30 mL), 1N NaOH (30 mL), brine (30 mL)
  3. dry with materialdried (MgSO4)
  4. filtrationThe solution was filtered
  5. concentrationconcentrated
  6. customto afford a yellow oil
  7. customchromatographed on silica gel eluting with 20% acetone in hexanes

Sources & evidence

ORD record
ord-b74536bb25b94b1f9ee1d3827013cb4e
Source dataset
uspto-grants-2005_03
Patent number
US06864266B2

Reaction notes

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