Sodium Bicarbonate → 2-{[[4-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-butyl]-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-4,5,6,7-tetrahydro-benzoimidazole-1-sulfonic acid dimethylamide

HRID 1624287Notes

Reaction equation

HRID 1624287 reaction equation
[CH3:1][N:2]([CH3:17])[S:3]([N:6]1[C:10]2[CH2:11][CH2:12][CH2:13][CH2:14][C:9]=2[N:8]=[C:7]1[CH:15]=O)(=[O:5])=[O:4].[N:18]1[C:27]2[CH:26]([NH:28][CH2:29][CH2:30][CH2:31][CH2:32][N:33]3[C:41](=[O:42])[C:40]4[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=4)[C:34]3=[O:43])[CH2:25][CH2:24][CH2:23][C:22]=2[CH:21]=[CH:20][CH:19]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH3:1][N:2]([CH3:17])[S:3]([N:6]1[C:10]2[CH2:11][CH2:12][CH2:13][CH2:14][C:9]=2[N:8]=[C:7]1[CH2:15][N:28]([CH2:29][CH2:30][CH2:31][CH2:32][N:33]1[C:34](=[O:43])[C:35]2[C:40](=[CH:39][CH:38]=[CH:37][CH:36]=2)[C:41]1=[O:42])[CH:26]1[C:27]2[N:18]=[CH:19][CH:20]=[CH:21][C:22]=2[CH2:23][CH2:24][CH2:25]1)(=[O:5])=[O:4]

Participants

6

Reactant 4

HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 589971372-[4-(5,6,7,8-Tetrahydroquinolin-8-ylamino)-butyl]-isoindole-1,3-dioneHCID 865903112-Formyl-4,5,6,7-tetrahydro-benzoimidazole-1-sulfonic acid dimethylamide

Product 1

HCID 691783352-{[[4-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-butyl]-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-4,5,6,7-tetrahydro-benzoimidazole-1-sulfonic acid dimethylamideYield 59.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-formyl-4,5,6,7-tetrahydro-benzoimidazole-1-sulfonic acid dimethylamide (0.3991 g, 1.5 mmol) and 2-[4-(5,6,7,8-tetrahydro-quinolin-8-ylamino)-butyl]-isoindole-1,3-dione (0.4424 g, 1.3 mmol) in CH2Cl2 (13 mL) was added sodium triacetoxyborohydride (0.5539 g, 2.6 mmol), and the reaction stirred at room temperature for 22 hours. Saturated NaHCO3 (20 mL) was added and the aqueous phase was extracted with CH2Cl2 (2×100 mL), and the combined organic extracts were washed with brine (1×75 mL), dried (NaSO4), and concentrated. Purification of the crude material by column chromatography on silica gel (33:1:1 CH2Cl2—MeOH—NH4OH) provided 0.4564 g (52%) of 2-{[[4-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-butyl]-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-4,5,6,7-tetrahydro-benzoimidazole-1-sulfonic acid dimethylamide as a yellow foam. 1H NMR (CDCl3) δ 1.28 (t, 2H, J=9 Hz), 1.49-1.52 (m, 2H), 1.74-1.81 (m, 6H), 1.91-2.00 (m, 1H), 2.11-2.20 (m, 1H), 2.50-2.73 (m, 7H), 2.92 (s, 2H), 2.95 (s, 4H), 3.52-3.57 (m, 2H), 4.17-4.22 (m, 2H), 4.32-4.37 (m, 1H), 4.81 (s, 1H), 6.95-6.98 (m, 1H), 7.27-7.28 (m, 1H), 7.68-7.70 (m, 2H), 7.79-7.82 (m, 2H), 8.32 (d, 1H, J=3 Hz).

Workup

  1. extractionthe aqueous phase was extracted with CH2Cl2 (2×100 mL)
  2. washthe combined organic extracts were washed with brine (1×75 mL)
  3. dry with materialdried (NaSO4)
  4. concentrationconcentrated
  5. customPurification of the crude material by column chromatography on silica gel (33:1:1 CH2Cl2—MeOH—NH4OH)

Sources & evidence

ORD record
ord-c94c015ce32947e3a568d2cb673359ae
Source dataset
uspto-grants-2014_07
Patent number
US08778967B2

Reaction notes

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