Potassium Iodide → 2-{[[4-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-butyl]-(5,6,7,8-tetrahydroquinoxalin-5-yl)-amino]-methyl}-benzoimidazole-1-carboxylic Acid Tert-Butyl Ester

HRID 1624314Notes

Reaction equation

HRID 1624314 reaction equation
[N:1]1[C:10]2[CH2:9][CH2:8][CH2:7][CH:6]([NH:11][CH2:12][CH2:13][CH2:14][CH2:15][N:16]3[C:24](=[O:25])[C:23]4[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=4)[C:17]3=[O:26])[C:5]=2[N:4]=[CH:3][CH:2]=1.[C:27]([O:31][C:32]([N:34]1[C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][C:37]=2[N:36]=[C:35]1[CH2:43]Cl)=[O:33])([CH3:30])([CH3:29])[CH3:28].[I-].[K+].C(N(C(C)C)CC)(C)C.C(=O)(O)[O-].[Na+]>CC#N>[C:27]([O:31][C:32]([N:34]1[C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][C:37]=2[N:36]=[C:35]1[CH2:43][N:11]([CH2:12][CH2:13][CH2:14][CH2:15][N:16]1[C:17](=[O:26])[C:18]2[C:23](=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:24]1=[O:25])[CH:6]1[CH2:7][CH2:8][CH2:9][C:10]2[N:1]=[CH:2][CH:3]=[N:4][C:5]1=2)=[O:33])([CH3:30])([CH3:29])[CH3:28]

Participants

7

Reactant 5

HCID 4875Potassium IodideHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 15829159tert-Butyl 2-(chloromethyl)-1H-benzimidazole-1-carboxylateHCID 691785752-[4-(5,6,7,8-Tetrahydro-quinoxalin-5-ylamino)-butyl]-isoindole-1,3-dione

Product 1

HCID 692063402-{[[4-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-butyl]-(5,6,7,8-tetrahydroquinoxalin-5-yl)-amino]-methyl}-benzoimidazole-1-carboxylic Acid Tert-Butyl EsterYield 85.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 2-[4-(5,6,7,8-tetrahydro-quinoxalin-5-ylamino)-butyl]-isoindole-1,3-dione (298 mg, 0.850 mmol) in CH3CN (12 mL) was added 2-chloromethyl-benzoimidazole-1-carboxylic acid tert-butyl ester (295 mg, 1.11 mmol), potassium iodide (14 mg), and diisopropylethylamine (0.296 ml, 1.70 mmol). The reaction mixture was stirred at 60° C. for 17 hours. Saturated sodium bicarbonate (15 mL) was added and the mixture was extracted with CH2Cl2 (3×30 mL). The combined organic extracts were dried (MgSO4), filtered and concentrated. Purification of the crude material by column chromatography on silica gel (1:10 EtOAc:hexanes then EtOAc then 1:10 McOH:EtOAc) provided the product as a clear oil (422 mg, 85%): 1H NMR (CDCl3): δ 1.34-1.43 (m, 2H), 1.48-1.60 (m, 2H), 1.68 (s, 9H), 1.71-1.81 (m, 1H), 1.88-1.97 (m, 1H), 2.00-2.21 (m, 2H), 2.60-2.69 (m, 1H), 2.76-2.93 (m, 3H), 3.55 (t, 2H, J=6.9 Hz), 4.29 (dd, 1H, J=9.6, 5.4 Hz), 4.46 (d, 1H, J=15.3 Hz), 4.61 (d, 1H, J=15.3 Hz), 7.19-7.24 (m, 2H), 7.63-7.69 (m, 3H), 7.74-7.81 (m, 3H), 8.18 (d, 1H, J=2.1 Hz), 8.27 (d, 1H, J=2.1 Hz).

Workup

  1. extractionthe mixture was extracted with CH2Cl2 (3×30 mL)
  2. dry with materialThe combined organic extracts were dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification of the crude material by column chromatography on silica gel (1:10 EtOAc

Sources & evidence

ORD record
ord-3bff4419c0e44de98d361cf0d8f27188
Source dataset
uspto-grants-2014_07
Patent number
US08778967B2

Reaction notes

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