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 216017

Reaction equation

HRID 216017 reaction equation
[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]

Participants

5

Reactant 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

Product 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}-amideYield 64.4%

Procedure

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 (10μ, 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).

Workup

  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 (10μ, 100 Å C18, column length 250×50 mm, gradient 90:10-0:100 H2O:MeCN)

Sources & evidence

ORD record
ord-dfa005756a3a4c07808d4f77fde552d7
Source dataset
uspto-grants-2012_06
Patent number
US08193191B2

Linked notes

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