Triethylamine → 1-(2,8-Dimethyl-1-thia-3,8-diazaspiro[4.5]dec-3-yl)-2-propylpentan-1-one

HRID 574623Notes

Reaction equation

HRID 574623 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.C(N(CC)CC)C.[C:20](Cl)(=[O:28])[CH:21]([CH2:25][CH2:26][CH3:27])[CH2:22][CH2:23][CH3:24]>ClCCl>[CH3:1][CH:2]1[N:6]([C:20](=[O:28])[CH:21]([CH2:25][CH2:26][CH3:27])[CH2:22][CH2:23][CH3:24])[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 8471TriethylamineHCID 762402-Propylvaleryl chlorideHCID 669939622,8-Dimethyl-1-thia-3,8-diazaspiro[4.5]decane

Product 1

HCID 468468011-(2,8-Dimethyl-1-thia-3,8-diazaspiro[4.5]dec-3-yl)-2-propylpentan-1-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

2,8-dimethyl-1-thia-3,8-diaza-spiro[4.5]decane (982 mg, 5.28 mmol) was dissolved in dry dichloromethane (5 ml) under argon atmosphere. Distilled triethylamine (1.10 ml, 7.92 mmol) was added and the resulting solution was cooled to 0° C. Valproyl chloride (910 mg, 5.60 mmol) was added dropwise with a syringe. The reaction flask was allowed to warm to room temperature with stirring, and white solid started to precipitate. After 4 h of stirring, dichloromethane (100 ml) was added and the resulting solution was washed with water (10 ml). The two phases were separated and the aqueous phase was extracted with dichloromethane (2×50 ml). The combined organic phase was dried with sodium sulfate, filtered and evaporated under reduced pressure. The residue was purified by flash chromatography (silica, CH2Cl2/EtOH/NH4OH 150/10/1) to give AF717 (521 mg, 99.2% chemical purity) as an off-white powder. 1H NMR (CDCl3, 300 MHz) δ 5.53, 5.26 (2q, J=6.12 and J=6.3 Hz, 1H, CHCH3), 4.67, 3.90 (2d, J=12.0 and J=11.35 Hz, 1H, CHHNCO), 3.48, 3.09 (2d, J=11.35 and J=12.0 Hz, 1H, CHHNCO), 2.78-2.59 (m, 2H, CH2N), 2.53-2.47 (m, 1H, CHCO), 2.30, 2.19 (2s, 3H, NCH3), 2.15-2.05 (m, 2H, CH2N), 2.02-1.84 (m, 2H, CH2CS), 1.74-1.61 (m, 4H, CH2CHCO), 1.55, 1.50 (2d, J=6.3 and J=6.12 Hz, 3H, CH3CH), 1.44-1.36 (m, 2H, CH2CS), 1.34-1.21 (m, 4H, CH2CH3), 0.93-0.87 (m, 6H, CH3CH2) ppm; 13C NMR (CDCl3, 300 MHz) δ 174.35, 174.04 (C), 59.13 (C), 57.35, 57.19 (CH), 54.52, 54.06 (CH2), 53.13, 52.77 (CH2), 46.09 (CH3), 43.77, 42.55 (CH), 38.37, 37.58 (CH2), 37.04, 36.20 (CH2), 35.76, 35.35 (CH2), 35.08, 34.77 (CH2), 26.01, 23.01 (CH3), 21.08, 20.98 (CH2), 20.73, 20.56 (CH2), 14.27, 14.22 (CH3) ppm.

Workup

  1. temperatureto warm to room temperature
  2. customto precipitate
  3. stirringAfter 4 h of stirring
  4. additiondichloromethane (100 ml) was added
  5. washthe resulting solution was washed with water (10 ml)
  6. customThe two phases were separated
  7. extractionthe aqueous phase was extracted with dichloromethane (2×50 ml)
  8. dry with materialThe combined organic phase was dried with sodium sulfate
  9. filtrationfiltered
  10. customevaporated under reduced pressure
  11. customThe residue was purified by flash chromatography (silica, CH2Cl2/EtOH/NH4OH 150/10/1)
  12. customto give AF717 (521 mg, 99.2% chemical purity) as an off-white powder

Sources & evidence

ORD record
ord-c3a2fe70d0934c74b307725af77c9e13
Source dataset
uspto-grants-2015_05
Patent number
US09034891B2

Reaction notes

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