Diisopropylethylamine → 5-Ethoxy-1,3-dihydro-1-[2-methoxy-4-(N-(1-ethoxycarbonyl-1-methylethyl)carbamoyl)benzenesulfonyl]-3-cyclohexyl-2H-benzimidazol-2-one

HRID 1081487Notes

Reaction equation

HRID 1081487 reaction equation
[CH2:1]([O:3][C:4]1[CH:33]=[CH:32][C:7]2[N:8]([S:18]([C:21]3[CH:26]=[CH:25][C:24]([C:27]([OH:29])=O)=[CH:23][C:22]=3[O:30][CH3:31])(=[O:20])=[O:19])[C:9](=[O:17])[N:10]([CH:11]3[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]3)[C:6]=2[CH:5]=1)[CH3:2].Cl.[CH2:35]([O:37][C:38]([C:40]([NH2:43])([CH3:42])[CH3:41])=[O:39])[CH3:36].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CCN(C(C)C)C(C)C>C(Cl)Cl>[CH2:1]([O:3][C:4]1[CH:33]=[CH:32][C:7]2[N:8]([S:18]([C:21]3[CH:26]=[CH:25][C:24]([C:27](=[O:29])[NH:43][C:40]([C:38]([O:37][CH2:35][CH3:36])=[O:39])([CH3:42])[CH3:41])=[CH:23][C:22]=3[O:30][CH3:31])(=[O:20])=[O:19])[C:9](=[O:17])[N:10]([CH:11]3[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]3)[C:6]=2[CH:5]=1)[CH3:2]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 152290425-Ethoxy-1,3-dihydro-1-(2-methoxy-4-carboxybenzenesulfonyl)-3-cyclohexyl-2H-benzimidazol-2-oneHCID 22343822Ethyl 2-amino-2-methylpropanoate hydrochloride

Product 1

HCID 152315545-Ethoxy-1,3-dihydro-1-[2-methoxy-4-(N-(1-ethoxycarbonyl-1-methylethyl)carbamoyl)benzenesulfonyl]-3-cyclohexyl-2H-benzimidazol-2-oneYield 27.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

500 mg of the compound obtained in Example 13, 300 mg of 1-ethoxycarbonyl-1-methylethylamine hydrochloride and 550 mg of BOP were mixed with 2 ml of DIPEA and 50 ml of DCM and the reaction medium was stirred for 30 minutes at room temperature. It was then concentrated under vacuum and the residue was taken up with water and then extracted with AcOEt, washed successively with 1N HCl , with 1N NaOH and then with water, dried over sodium sulfate and concentrated under vacuum. The residue was purified by chromatography on a silica column using a DCM/AcOEt mixture (97/3; v/v) as the eluent. 170 mg of the expected product were obtained in the form of a white solid by crystallization from an AcOEt/iso ether mixture (10/90; v/v). M.p.=202° C.

Workup

  1. concentrationIt was then concentrated under vacuum
  2. extractionextracted with AcOEt
  3. washwashed successively with 1N HCl , with 1N NaOH
  4. dry with materialwith water, dried over sodium sulfate
  5. concentrationconcentrated under vacuum
  6. customThe residue was purified by chromatography on a silica column

Sources & evidence

ORD record
ord-a8d318676ce343a2b245285fe8c3eb86
Source dataset
uspto-grants-1996_12
Patent number
US05585394

Reaction notes

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