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

HRID 42328

반응식

HRID 42328 반응식
[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.[O:45]1[CH:49]=[CH:48][C:47]([CH:50]=O)=[CH:46]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.C[N+](C)(C)C>>[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][N:37]([CH2:50][C:47]4[CH:48]=[CH:49][O:45][CH:46]=4)[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]

참가 물질

5

반응물 4

HCID 63651,1-DichloroethaneHCID 103513-FuraldehydeHCID 13696215Tetramethylammonium Triacetoxyborohydride (>90%)HCID 44596869(R)-N-(4-(3,4-dimethoxyphenyl)-4-(1,3-dioxo-4-(piperazin-1-yl)isoindolin-2-yl)butyl)thiophene-2-sulfonamide

생성물 1

HCID 58296044(r)-Thiophene-2-sulfonic acid {4-(3,4-dimethoxy-phenyl)-4-[4-(4-furan-3-ylmethyl-piperazin-1-yl)-1,3-dioxo-1,3-dihydro-isoindol-2-yl]-butyl}-amide수율 64.4%

실험 절차

A 50-mL round bottom flask was charged with Compound 167 (20.0 mg, 0.032 mmol) and dichloroethane (4.0 mL). Trietheylamine (5.0 μL) was added followed by 3-furaldehyde (6.0 mg, 0.06 mmol) and tetramethylammonium triacetoxyborohydride (11.8 mg, 0.045 mmol). The mixture was stirred at room temperature for 3 h. The mixture 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 90:10-0:100 H2O:MeCN) to give 13.7 mg of Compound 170 as a yellow solid. 1H NMR (300 MHz, CDCl3) δ 7.50-7.64 (m, 5 H), 7.43 (d, J=7.2 Hz, 1 H), 7.13 (d, J=8.2 Hz, 1 H), 7.00-7.06 (m, 3 H), 6.79 (d, J=8.0 Hz, 1 H), 6.56 (s, 1 H), 5.12-5.23 (m, 1 H), 4.61-4.74 (m, 1 H), 3.87 (s, 3 H), 3.84 (s, 3 H), 3.63-3.75 (m, 4 H), 3.41-3.51 (m, 2 H), 2.94-3.35 (m, 4 H), 2.53-2.65 (m, 1 H), 2.18-2.30 (m, 1 H), and 1.46-1.71 (m, 2 H); MS (ES+) 665 (M+1).

후처리

  1. additionTrietheylamine (5.0 μL) was added
  2. customThe mixture quenched with saturated aqueous sodium bicarbonate (10 mL)
  3. extractionextracted with dichloromethane (50 mL)
  4. customThe organic layer was dried
  5. filtrationfiltered through Celite®
  6. concentrationconcentrated in vacuo
  7. 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 90:10-0:100 H2O:MeCN)

출처 및 근거

ORD 기록
ord-080b50773ff6453e8b3d08c788addd4a
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08536174B2

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