1H-Indole-3-propanoic acid → AF-710B

HRID 574621Notes

Reaction equation

HRID 574621 reaction equation
[CH3:1][CH:2]1[NH:6][CH2:5][C:4]2([CH2:11][CH2:10][N:9]([CH3:12])[CH2:8][CH2:7]2)[S:3]1.C1(N=C=NC2CCCCC2)CCCCC1.[NH:28]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[C:30]([CH2:37][CH2:38][C:39](O)=[O:40])=[CH:29]1>ClCCl>[CH3:1][CH:2]1[N:6]([C:39](=[O:40])[CH2:38][CH2:37][C:30]2[C:31]3[C:36](=[CH:35][CH:34]=[CH:33][CH:32]=3)[NH:28][CH:29]=2)[CH2:5][C:4]2([CH2:11][CH2:10][N:9]([CH3:12])[CH2:8][CH2:7]2)[S:3]1

Participants

5

Reactant 3

HCID 37441H-Indole-3-propanoic acidHCID 10868DicyclohexylcarbodiimideHCID 669939622,8-Dimethyl-1-thia-3,8-diazaspiro[4.5]decane

Product 1

HCID 58516166AF-710B

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 2,8-dimethyl-1-thia-3,8-diaza-spiro[4.5]decane (2.18 g, 11.7 mmol) in dichloromethane (230 ml) at room temperature was added dicyclohexylcarbodiimide (DCC) (3.24 g, 15.7 mmol) followed by addition of 3-indolepropionic acid (2.87 g, 15.2 mmol). The resulting solution was stirred at room temperature overnight. During the reaction a white solid precipitated. After filtration the solvent was evaporated and the crude product was purified by flash chromatography (silica, CH2Cl2/EtOH/NH4OH 90/10/1) to give AF710 (2.5 g, 100% chemical purity) as a white solid. 1H NMR (CDCl3, 300 MHz) δ 8.17 (br s, 1H, NH-indole), 7.60 (d, J=7.81 Hz, 1H, CHC arom), 7.35 (d, J=8.08 Hz, 1H, CHC arom), 7.19 (app t, J=7.53 Hz, 1H, CHCH arom), 7.12 (app t, J=7.45 Hz, 1H, CHCH arom), 7.02 (d, J=1.86 Hz, 1H, CHNH arom), 5.52, 5.09 (2q, J=6.15 and J=6.22 Hz, 1H, CHCH3), 4.62, 3.66 (2d, J=11.76 and J=11.5 Hz, 1H, CHHNCO), 3.29, 3.08 (2d, J=11.48 and J=12.0 Hz, 1H, CHHNCO), 3.18-3.11 (m, 2H), 2.72-2.66 (m, 2H), 2.64-2.46 (m, 2H), 2.26, 2.25 (2s, 3H, NCH3), 2.32-2.19, 2.12-2.02 (2m, 2H), 1.87-1.80, 1.68-1.51 (2m, 4H), 1.48, 1.43 (2d, J=6.21 and J=6.19 Hz, 3H, CH3—CH) ppm; 13C NMR (CDCl3, 500 MHz) δ 170.58 (C), 136.39 (C), 127.25 (C), 122.19 (CH), 121.80 (CH), 119.52 (CH), 118.73 (CH), 115.17 (C), 111.31 (CH), 57.48, 57.19 (CH), 55.46 (C), 54.55, 54.12 (CH2), 53.11, 52.86 (CH2), 46.21, 46.15 (CH3), 38.05, 37.32 (CH2), 36.82, 36.31 (CH2), 34.41 (CH2), 25.44, 23.47 (CH3), 21.04, 20.96 (CH2) ppm.

Workup

  1. customDuring the reaction a white solid
  2. customprecipitated
  3. filtrationAfter filtration the solvent
  4. customwas evaporated
  5. customthe crude product was purified by flash chromatography (silica, CH2Cl2/EtOH/NH4OH 90/10/1)
  6. customto give AF710 (2.5 g, 100% chemical purity) as a white solid

Sources & evidence

ORD record
ord-2654224d5aef4a0985205d7aa32ceca2
Source dataset
uspto-grants-2015_05
Patent number
US09034891B2

Reaction notes

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