巯基丁二酸 → [3-(2-Carbamoyl-ethyl)-4-oxo-2-(5-phenylethynyl-thiophen-2-yl)-thiazolidin-5-yl]-acetic acid

HRID 2230805

反应方程式

HRID 2230805 反应方程式
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]

参与物

6

反应物 4

HCID 6268巯基丁二酸HCID 81531N,N-二异丙基乙胺HCID 27371405-(2-苯乙基-1-基)噻吩-2-甲苯HCID 22222288BETA-丙胺酰胺盐酸盐

产物 1

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

试剂、催化剂与溶剂 1

HCID 6342乙腈溶剂

实验过程

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.

后处理

  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

来源与证据

ORD记录
ord-5122c6a9535b45f09804b58dd454ccf1
来源数据集
uspto-grants-2002_07
专利号
US06426357B1

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