1H-Indole-3-propanoic acid → Dichloromethane isopropanol ammonium hydroxide

HRID 574629Notes

Reaction equation

HRID 574629 reaction equation
[CH3:1][CH:2]1[CH2:6][NH:5][C:4]2([CH2:11][CH2:10][N:9]([CH3:12])[CH2:8][CH2:7]2)[O:3]1.[NH:13]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:15]([CH2:22][CH2:23][C:24]([OH:26])=[O:25])=[CH:14]1.C1(N=C=NC2CCCCC2)CCCCC1.CN(C1C=CC=CN=1)C.[Cl:51][CH2:52][Cl:53]>>[CH2:52]([Cl:53])[Cl:51].[CH3:1][CH:2]([OH:3])[CH3:6].[NH4+:5].[OH-:25].[CH3:1][CH:2]1[CH2:6][N:5]([C:24](=[O:26])[CH2:23][CH2:22][C:15]2[C:16]3[C:21](=[CH:20][CH:19]=[CH:18][CH:17]=3)[NH:13][CH:14]=2)[C:4]2([CH2:11][CH2:10][N:9]([CH3:12])[CH2:8][CH2:7]2)[O:3]1

Participants

7

Reactant 5

HCID 37441H-Indole-3-propanoic acidHCID 6344DichloromethaneHCID 10868DicyclohexylcarbodiimideHCID 218852-DimethylaminopyridineHCID 220974902,8-Dimethyl-1-oxa-4,8-diazaspiro[4.5]decane

Product 2

HCID 18971915Dichloromethane isopropanol ammonium hydroxideHCID 468468121-(2,8-dimethyl-1-oxa-4,8-diazaspiro[4.5]dec-4-yl)-3-(1H-indol-3-yl)-propan-1-one

Procedure

A solution of 2,8-dimethyl-1-oxa-4,8-diazaspiro[4.5]decane (1.09 g, 6.41 mmol), 3-indolepropionic acid (1.57 g, 8.3 mmol), dicyclohexylcarbodiimide (DCC, 1.78 g, 8.65 mmol) and dimethylaminopyridine (DMAP, 0.78 g, 6.41 mol) in dichloromethane (100 ml) was stirred at room temperature for 4 days. The precipitate was removed by filtration and the solvent was evaporated. Flash chromatography (silica, CH2Cl2/i-PrOH/NH4OH 85/15/1) gave the title compound that was triturated in ether. The obtained white solid (AF706), 1.1 gr (99.4% chemical purity), was filtered and dried. 1H-NMR (CDCl3, 300 MHz) δ 8.15 (br NH), 7.63 (d, J=7.76 Hz, 1H, ArH), 7.38 (d, J=7.98 Hz, 1H, ArH), 7.23 (dt, J=1.12, 7.56 Hz, 1H, ArH), 7.13 (dt, J=1.07, 7.44 Hz, 1H, ArH), 7.08 (d, J=2.15 Hz, 1H, NCHC), 4.05 (m, 1H, OCH), 3.53 (dd, J=9.0, 5.5 Hz, 1H, NCHH), 3.13 (m, 3H), 2.96 (t, J=9.2 Hz, 1H), 2.80-2.70 (m, 3H), 2.61-2.70 ((m, 2H), 2.23-2.34 (m, 2H, CH2-piperidine), 2.31 (s, 3H, NCH3), 1.37 (m, 1H, CH-piperidine), 1.33 (m, 1H, CH-piperidine), 1.25 (d, J=6.0 Hz, 3H, CH3) ppm; 13C-NMR (CDCl3, 300 MHz) δ 169.66 (C), 136.52 (C), 122.49 (CH), 121.90 (CH), 119.24 (CH), 118.78 (CH), 115.18 (C), 111.41 (CH), 94.16 (C), 69.92 (CH), 53.25 (CH2), 52.84 (CH2), 52.70 (CH2), 45.99 (CH3), 37.52 (CH2), 33.66 (CH2), 30.90 (CH2), 20.73 (CH2), 18.26 (CH3) ppm.

Workup

  1. customThe precipitate was removed by filtration
  2. customthe solvent was evaporated

Sources & evidence

ORD record
ord-e8745d8b4cf647cb9599fd8675dc111e
Source dataset
uspto-grants-2015_05
Patent number
US09034891B2

Reaction notes

Loading…