Dicyclohexylcarbodiimide → 1-(2,8-Dimethyl-1-thia-3,8-diazaspiro[4.5]dec-3-yl)-3-(1-methyl-indol-3-yl)propan-1-one

HRID 1187328Notes

Reaction equation

HRID 1187328 reaction equation
C1(N=C=NC2CCCCC2)CCCCC1.[CH3:16][N:17]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:19]([CH2:26][CH2:27][C:28]([OH:30])=O)=[CH:18]1.[CH3:31][CH:32]1[NH:36][CH2:35][C:34]2([CH2:41][CH2:40][N:39]([CH3:42])[CH2:38][CH2:37]2)[S:33]1>ClCCl>[CH3:31][CH:32]1[N:36]([C:28](=[O:30])[CH2:27][CH2:26][C:19]2[C:20]3[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=3)[N:17]([CH3:16])[CH:18]=2)[CH2:35][C:34]2([CH2:41][CH2:40][N:39]([CH3:42])[CH2:38][CH2:37]2)[S:33]1

Participants

5

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 3446003-(1-methyl-1H-indol-3-yl)propanoic acidHCID 669939622,8-Dimethyl-1-thia-3,8-diazaspiro[4.5]decane

Product 1

HCID 468465221-(2,8-Dimethyl-1-thia-3,8-diazaspiro[4.5]dec-3-yl)-3-(1-methyl-indol-3-yl)propan-1-oneYield 32.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of dicyclohexylcarbodiimide (DCC) (1.3 g, 6.3 mmol) in dichloromethane (50 ml) at room temperature was added 3-(1-methyl-indole-3-yl)propanoic acid (1.18 g, 5.8 mmol) and a solution of 2,8-dimethyl-1-thia-3,8-diaza-spiro[4.5]decane (1.2 g, 6.4 mmol) in dichloromethane (50 ml). The resulting solution was stirred at room temperature for 48 h. 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 100/10/1) to give the title compound (0.7 g) as a colorless oil. 1H NMR (CDCl3, 300 MHz) δ 7.60 (d, J=7.82 Hz, 1H, CHC arom), 7.35-7.2 (m, 2H, 2CHC arom), 7.23 (dt, J=1.06, 7.45 Hz, 1H, CHCH arom), 6.90 (s, 1H, CHNH arom), 5.54, 5.07 (2q, J=6.16 and J=6.25 Hz, 1H, CHCH3), 4.63, 3.68 (2d, J=12.0 and J=11.5 Hz, 1H, CHHNCO), 3.75, 3.74 (2s, 3H, NCH3), 3.32 (d, J=11.5 Hz, 0.6H, CHHNCO), 3.17-3.05 (m, 2.4H), 2.8-2.4 (m), 2.68 [t, J=7.6 Hz, C(O)CH2], 2.28, 2.26 (2s, 3H, NCH3), 2.3-2.2 (m), 2.1-2.0 (m), 2.0-1.8 (m), 1.7-1.4 (m), 1.48, 1.43 (2d, J=6.18 and J=6.26 Hz, 3H, CH3—CH) ppm; 13C NMR (CDCl3, 300 MHz) δ 170.6 (C), 137.1 (C), 126.8 (C), 126.7 (CH), 121.8 (CH), 119.0 (CH), 118.9 (CH), 113.7 (C), 109.4 (CH), 59.0 (C), 57.5, 57.2 (CH), 54.6, 54.2 (CH2), 53.2, 52.9 (CH2), 46.3, 46.2 (CH3), 38.1, 37.4 (CH2), 36.9, 36.6 (CH2), 36.4, 34.7 (CH2), 32.7 (CH3), 25.5, 23.5 (CH3), 21.0, 20.9 (CH2) ppm.

Workup

  1. customDuring the reaction a white solid
  2. customprecipitated
  3. filtrationAfter filtration
  4. customthe solvent was evaporated
  5. customthe crude product was purified by flash chromatography (silica, CH2Cl2/EtOH/NH4OH 100/10/1)

Sources & evidence

ORD record
ord-3da0feb1fe6c4922bf2c7f56c709c128
Source dataset
uspto-grants-2014_03
Patent number
US08673931B2

Reaction notes

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