(+-)-Mercaptosuccinic acid → [3-(2-Carbamoyl-ethyl)-4-oxo-2-(5-phenylethynyl-thiophen-2-yl)-thiazolidin-5-yl]-acetic acid

HRID 2230805

Reaction equation

HRID 2230805 reaction equation
Cl.[NH2:2][CH2:3][CH2:4][C:5]([NH2:7])=[O:6].[C:8]1([C:14]#[C:15][C:16]2[S:20][C:19]([CH:21]=O)=[CH:18][CH:17]=2)[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[SH:23][CH:24]([CH2:28][C:29]([OH:31])=[O:30])[C:25](O)=[O:26].C(N(C(C)C)CC)(C)C>C(#N)C>[C:5]([CH2:4][CH2:3][N:2]1[C:25](=[O:26])[CH:24]([CH2:28][C:29]([OH:31])=[O:30])[S:23][CH:21]1[C:19]1[S:20][C:16]([C:15]#[C:14][C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)=[CH:17][CH:18]=1)(=[O:6])[NH2:7]

Participants

6

Reactant 4

HCID 6268(+-)-Mercaptosuccinic acidHCID 81531DiisopropylethylamineHCID 27371405-(Phenylethynyl)thiophene-2-carbaldehydeHCID 222222883-Aminopropanamide hydrochloride

Product 1

HCID 86758382[3-(2-Carbamoyl-ethyl)-4-oxo-2-(5-phenylethynyl-thiophen-2-yl)-thiazolidin-5-yl]-acetic acid

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of β-alanine amide hydrochloride (3.11 g, 25 mmol), 5-(phenylethynyl)thiophene-2-carboxaldehyde (5.31 g, 25 mmol), mercaptosuccinic acid (11.26 g, 75 mmol) and diisopropylethylamine (3.6 g, 27.5 mmol) was stirred in acetonitrile (300 mL) at reflux for forty eight hours. The solvent was evaporated and the residue was shaken with 2 N HCl (500 mL) and ethyl acetate (3×200 mL) The ethyl acetate solution was washed with water then brine and dried (MgSO4) and evaporated. The product was purified on a 600 mL. silica dry column by elution with dichloromethane:acetic acid (99:1) followed by dichloromethane:methanol:acetic acid (95:5:1). The appropriate fractions were evaporated. The residue was washed with ether and dried to provide the title compound as a white solid: (2.44 g, 23.5%): m.p. 175-178. 1H-NMR (DMSO-d6) δ 12.6 (broad, 1H), 7.56-7.57 (d, 1H, J=2.4 Hz), 7.54-7.55 (d, 1H, J=3.6 Hz), 7.4-7.46 (m, 4H), 7.28-7.32 (m, 2H), 6.90(s, 1H), 6.15 (s, 0.5 H), 6.12-6.13 (d, 0.5H, J=1.6 Hz), 4.24-4.28 (m, 1H), 4.15-4.19 (dd, 0.5H, J=3.6 Hz), 2.97-3.09 (m, 1H), 2.64-2.74 (m, 1H), 2.36-2.46 (m, 1H), 2.08-2.21 (m, 1H); MS(ESI) 413[M-H], 415[M+H]. Analytical HPLC; Capcell Pak C18, 30% acetonitrile: 70% 0.1% aqueous TFA.51 trans: 49 cis. FTIR (ATR) 1650, 1720 cm−1. Anal. (C20H18N2O4S2) calc. C, 57.95; H, 4.38; N, 6.76. obs. C, 57.59; H, 4.34; N, 6.56.

Workup

  1. temperatureat reflux for forty eight hours
  2. customThe solvent was evaporated
  3. washwas washed with water
  4. dry with materialbrine and dried (MgSO4)
  5. customevaporated
  6. customThe product was purified on a 600 mL
  7. customsilica dry column
  8. washby elution with dichloromethane:acetic acid (99:1)
  9. customThe appropriate fractions were evaporated
  10. washThe residue was washed with ether
  11. customdried

Sources & evidence

ORD record
ord-5122c6a9535b45f09804b58dd454ccf1
Source dataset
uspto-grants-2002_07
Patent number
US06426357B1

Linked notes

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