1,1-Dichloroethane → (r)-Thiophene-2-sulfonic acid [4-[4-(4-cyclopentyl-piperazin-1-yl)-1,3-dioxo-1,3-dihydro-isoindol-2-yl]-4-(3,4-dimethoxy-phenyl)-butyl]-amide

HRID 42329

Reaktionsgleichung

Reaktionsgleichung von HRID 42329
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C@H:11]([N:24]2[C:32](=[O:33])[C:31]3[C:26](=[CH:27][CH:28]=[CH:29][C:30]=3[N:34]3[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]3)[C:25]2=[O:40])[CH2:12][CH2:13][CH2:14][NH:15][S:16]([C:19]2[S:20][CH:21]=[CH:22][CH:23]=2)(=[O:18])=[O:17])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].ClC(Cl)C.C(N(CC)CC)C.[C:52]1(=O)[CH2:56][CH2:55][CH2:54][CH2:53]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>>[CH:52]1([N:37]2[CH2:38][CH2:39][N:34]([C:30]3[CH:29]=[CH:28][CH:27]=[C:26]4[C:31]=3[C:32](=[O:33])[N:24]([C@@H:11]([C:5]3[CH:6]=[CH:7][C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=3)[CH2:12][CH2:13][CH2:14][NH:15][S:16]([C:19]3[S:20][CH:21]=[CH:22][CH:23]=3)(=[O:18])=[O:17])[C:25]4=[O:40])[CH2:35][CH2:36]2)[CH2:56][CH2:55][CH2:54][CH2:53]1

Komponenten

6

Edukt 5

HCID 63651,1-DichloroethaneHCID 8452CyclopentanoneHCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 44596869(R)-N-(4-(3,4-dimethoxyphenyl)-4-(1,3-dioxo-4-(piperazin-1-yl)isoindolin-2-yl)butyl)thiophene-2-sulfonamide

Produkt 1

HCID 58295863(r)-Thiophene-2-sulfonic acid [4-[4-(4-cyclopentyl-piperazin-1-yl)-1,3-dioxo-1,3-dihydro-isoindol-2-yl]-4-(3,4-dimethoxy-phenyl)-butyl]-amideAusbeute 48,8 %

Versuchsvorschrift

A 50-mL round bottom flask was charged with Compound 167 (10.0 mg, 0.016 mmol) and dichloroethane (2.3 mL). Triethylamine (2.5 μL, 0.018 mmol) was added followed by cyclopentanone (7.1 μL, 0.06 mmol) and sodium triacetoxyborohydride (4.7 mg, 0.022 mmol). The mixture was stirred at room temperature for 3 h. The mixture was quenched with saturated aqueous sodium bicarbonate (10 mL) and extracted with dichloromethane (50 mL). The organic layer was dried using Na2SO4, filtered through Celite®, and concentrated in vacuo. The crude oil was purified on a on a Gilson HPLC with a reversed phase Kromasil column (10 u, 100 Å C18, column length 250×50 mm, gradient 75:25-0:100 H2O:MeCN) to give 5.1 mg of Compound 193 as a yellow solid. 1H NMR (300 MHz, CDCl3) δ 7.53-7.64 (m, 3 H), 7.44 (d, J=7.2 Hz, 1 H), 7.14 (d, J=8.2 Hz, 1 H), 6.91-7.06 (m, 3 H), 6.79 (d, J=8.0 Hz, 1 H), 6.56 (s, 1 H), 5.13-5.19 (m, 1 H), 4.51-4.64 (m, 1 H), 3.88 (s, 3 H), 3.85 (s, 3 H), 3.73-3.83 (m, 2 H), 3.42-3.64 (m, 2 H), 2.78-3.22 (m, 6 H), 2.48-2.61 (m, 1 H), 1.88-2.31 (m, 4 H), 1.47-1.69 (m, 4 H), and 1.27-1.33 (m, 4 H); MS (ES+) 653 (M+1).

Aufarbeitung

  1. customThe mixture was quenched with saturated aqueous sodium bicarbonate (10 mL)
  2. extractionextracted with dichloromethane (50 mL)
  3. customThe organic layer was dried
  4. filtrationfiltered through Celite®
  5. concentrationconcentrated in vacuo
  6. customThe crude oil was purified on a on a Gilson HPLC with a reversed phase Kromasil column (10 u, 100 Å C18, column length 250×50 mm, gradient 75:25-0:100 H2O:MeCN)

Quellen und Nachweise

ORD-Eintrag
ord-714ec9ee7aee4400a07bd32b2da41de7
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08536174B2

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