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 216018

反応式

HRID 216018 の反応式
[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

参加物

6

反応物 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

生成物 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]-amide収率 48.8%

実験手順

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 (10μ, 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, 1H), 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, 6H), 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).

後処理

  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 (10μ, 100 Å C18, column length 250×50 mm, gradient 75:25-0:100 H2O:MeCN)

出典と根拠

ORDレコード
ord-81d555c2089843b49921ebc96fa69be2
出典データセット
uspto-grants-2012_06
特許番号
US08193191B2

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