Potassium Iodide → HCID 178454035, compound

HRID 899772Notes

Reaction equation

HRID 899772 reaction equation
[C:1]([O:5][C:6](=[O:25])[NH:7][C@H:8]1[CH2:13][CH2:12][C@H:11]([NH:14][C@@H:15]2[C:24]3[N:23]=[CH:22][CH:21]=[CH:20][C:19]=3[CH2:18][CH2:17][CH2:16]2)[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[C:26]([O:30][C:31]([N:33]1[C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][C:36]=2[N:35]=[C:34]1[CH2:42]Cl)=[O:32])([CH3:29])([CH3:28])[CH3:27].C(N(C(C)C)CC)(C)C.[I-].[K+]>C(#N)C>[C:26]([O:30][C:31]([N:33]1[C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][C:36]=2[N:35]=[C:34]1[CH2:42][N:14]([C@H:11]1[CH2:12][CH2:13][C@H:8]([NH:7][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:25])[CH2:9][CH2:10]1)[CH:15]1[C:24]2[N:23]=[CH:22][CH:21]=[CH:20][C:19]=2[CH2:18][CH2:17][CH2:16]1)=[O:32])([CH3:29])([CH3:28])[CH3:27]

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 81531DiisopropylethylamineHCID 15829159tert-Butyl 2-(chloromethyl)-1H-benzimidazole-1-carboxylateHCID 178454036HCID 178454036, compound

Product 1

HCID 178454035HCID 178454035, compoundYield 56%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

To a suspension of [4-((S)-5,6,7,8-tetrahydro-quinolin-8-ylamino)-trans-cyclohexyl]-carbamic acid tert-butyl ester (1.95 g, 5.64 mmol) in dry acetonitrile (60 mL) was added 2-chloromethyl-benzoimidazole-1-carboxylic acid tert-butyl ester (1.65 g, 6.20 mmol), diisopropylethylamine (2.0 mL, 11.4 mmol) and potassium iodide (100 mg, 0.60 mmol). The mixture was warmed to 60° C. and stirred for 2 days under nitrogen. The mixture was concentrated, dissolved in methylene chloride (80 mL) and washed with brine (50 mL). The aqueous layer was extracted with methylene chloride (3×50 mL). The combined organic layers were dried (Na2SO4) and concentrated. The crude mixture was purified by column chromatography on silica gel (80 g) with methanol/methylene chloride (4:96) to afford 2-{[(4-tert-butoxycarbonylamino-trans-cyclohexyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzimidazole-1-carboxylic acid tert-butyl ester as a white solid (1.82 g, 56%). 1H NMR (CDCl3) δ 1.09 (bs, 2H), 1.43 (s, 9H), 1.68 (s, 9H), 1.83-2.14 (m, 6H), 2.47-2.63 (m, 1H), 2.65-2.79 (m, 1H), 2.79-2.95 (m, 1H), 3.32 (bs, 1H), 4.30 (bs, 2H), 4.46 (s, 2H), 6.75-6.89 (m, 1H), 7.00-7.13 (m, 1H), 7.61-7.70 (m, 1H), 7.70-7.79 (m, 1H), 8.32 (bs, 1H).

Workup

  1. concentrationThe mixture was concentrated
  2. dissolutiondissolved in methylene chloride (80 mL)
  3. washwashed with brine (50 mL)
  4. extractionThe aqueous layer was extracted with methylene chloride (3×50 mL)
  5. dry with materialThe combined organic layers were dried (Na2SO4)
  6. concentrationconcentrated
  7. customThe crude mixture was purified by column chromatography on silica gel (80 g) with methanol/methylene chloride (4:96)

Sources & evidence

ORD record
ord-aaf982f6aa2a491a95cb4335074206ba
Source dataset
uspto-grants-2008_04
Patent number
US07354934B2

Reaction notes

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