Diisopropylethylamine → 2-{[(S)-((Z)-4-tert-butoxycarbonylamino-but-2-enyl)-5,6,7,8-tetrahydro-quinolin-8-yl-amino]-methyl}-benzimidazole-1-carboxylic acid tert-butyl ester

HRID 899635Notes

Reaction equation

HRID 899635 reaction equation
[C:1]([O:5][C:6](=[O:13])[NH:7][CH2:8][CH:9]=[CH:10][CH2:11]Cl)([CH3:4])([CH3:3])[CH3:2].C(N(C(C)C)CC)(C)C.[C:23]([O:27][C:28]([N:30]1[C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][C:33]=2[N:32]=[C:31]1[CH2:39][NH:40][CH:41]1[C:50]2[N:49]=[CH:48][CH:47]=[CH:46][C:45]=2[CH2:44][CH2:43][CH2:42]1)=[O:29])([CH3:26])([CH3:25])[CH3:24]>C(#N)C.[I-].[K+]>[C:23]([O:27][C:28]([N:30]1[C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][C:33]=2[N:32]=[C:31]1[CH2:39][N:40]([CH2:11]/[CH:10]=[CH:9]\[CH2:8][NH:7][C:6]([O:5][C:1]([CH3:2])([CH3:4])[CH3:3])=[O:13])[C@@H:41]1[C:50]2[N:49]=[CH:48][CH:47]=[CH:46][C:45]=2[CH2:44][CH2:43][CH2:42]1)=[O:29])([CH3:26])([CH3:24])[CH3:25]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 219850812-[(5,6,7,8-Tetrahydroquinolin-8-ylamino)-methyl]-benzimidazole-1-carboxylic acid tert-butyl esterHCID 71438464(4-Chloro-but-2-enyl)-carbamic acid tert-butyl ester

Product 1

HCID 692939962-{[(S)-((Z)-4-tert-butoxycarbonylamino-but-2-enyl)-5,6,7,8-tetrahydro-quinolin-8-yl-amino]-methyl}-benzimidazole-1-carboxylic acid tert-butyl esterYield 161.1%

Reagents, catalysts & solvents 2

HCID 4875Potassium IodideCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

(4-Chloro-but-2-enyl)-carbamic acid tert-butyl ester (1.81 g, 7.47 mmol), potassium iodide (59 mg, 0.36 mmol) and diisopropylethylamine (1.80 mL, 10.3 mmol) were added to a solution of 2-[(5,6,7,8-tetrahydroquinolin-8-ylamino)-methyl]-benzimidazole-1-carboxylic acid tert-butyl ester (2.57 g, 6.79 mmol)) in acetonitrile (70 mL) and warmed to 60° C. and stirred for 17 h under nitrogen. The solvent was removed in vacuo. The residue was dissolved in methylene chloride (100 mL) and washed with brine (100 mL). The aqueous layer was extracted with methylene chloride (2×150 mL). The combined organic layers were dried (Na2SO4) and concentrated. The crude mixture was purified by column chromatography on silica gel (150 g) to afford 2-{[(S)-((Z)-4-tert-butoxycarbonylamino-but-2-enyl)-5,6,7,8-tetrahydro-quinolin-8-yl-amino]-methyl}-benzimidazole-1-carboxylic acid tert-butyl ester (5.99 g, 88%) as a white foamy solid. 1H NMR (CDCl3) δ 1.43 (s, 9H), 1.72 (s, 9H), 1.95-2.08 (m, 4H), 2.09-2.20 (m, 1H), 2.61 (d, 1H, J=16.2 Hz), 3.28 (dd, 1H, J=14.1, 5.4 Hz), 3.62 (dd, 1H, J=13.7, 7.2 Hz), 3.69-3.85 (m, 2H), 4.29 (dd, 1H, J=9.2, 6.6 Hz), 4.42 (d, 1H, J=14.9 Hz), 4.48 (d, 1H, J=14.9 Hz), 5.43-5.63 (m, 2H), 6.19 (s, 1H), 6.87 (dd, 1H, J=7.5, 4.8 Hz), 7.17 (d, 1H, J=7.7 Hz), 7.23-7.28 (m, 1H), 7.65-7.71 (m, 1H), 7.75-7.80 (m, 1H), 8.34 (d, 1H, J=4.4 Hz).

Workup

  1. customThe solvent was removed in vacuo
  2. dissolutionThe residue was dissolved in methylene chloride (100 mL)
  3. washwashed with brine (100 mL)
  4. extractionThe aqueous layer was extracted with methylene chloride (2×150 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 (150 g)

Sources & evidence

ORD record
ord-a554f619084747708fc8575284fb085a
Source dataset
uspto-grants-2008_04
Patent number
US07354932B2

Reaction notes

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