1,1'-Carbonyldiimidazole → tert-butyl (S)-2-(3-(3-(2-(methoxycarbonylamino)ethoxy)-3-(3-chlorophenyl)propyl)-3-methylureido)-3-cyclohexylpropyl(methyl)carbamate

HRID 426071Notes

Reaction equation

HRID 426071 reaction equation
C1N=CN([C:6]([N:8]2[CH:12]=N[CH:10]=[CH:9]2)=[O:7])C=1.[NH2:13][C@@H:14]([CH2:25][CH:26]1[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1)[CH2:15][N:16]([CH3:24])[C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20].CCN(C(C)C)C(C)C.[Cl:41][C:42]1[CH:43]=[C:44]([CH:48]([O:53][CH2:54][CH2:55][NH:56][C:57](=[O:60])[O:58][CH3:59])CCNC)[CH:45]=[CH:46][CH:47]=1>C(Cl)Cl>[CH3:59][O:58][C:57]([NH:56][CH2:55][CH2:54][O:53][CH:48]([C:44]1[CH:45]=[CH:46][CH:47]=[C:42]([Cl:41])[CH:43]=1)[CH2:10][CH2:9][N:8]([CH3:12])[C:6](=[O:7])[NH:13][C@@H:14]([CH2:25][CH:26]1[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31]1)[CH2:15][N:16]([CH3:24])[C:17](=[O:23])[O:18][C:19]([CH3:21])([CH3:22])[CH3:20])=[O:60]

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 59201313tert-butyl (S)-2-amino-3-cyclohexylpropylmethylcarbamateHCID 59364348Methyl 2-(1-(3-chlorophenyl)-3-(methylamino)propoxy)ethylcarbamate

Product 1

HCID 86642388tert-butyl (S)-2-(3-(3-(2-(methoxycarbonylamino)ethoxy)-3-(3-chlorophenyl)propyl)-3-methylureido)-3-cyclohexylpropyl(methyl)carbamateYield 50%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

At 0° C., CDI (48.6 mg, 0.3 mmol) was added to a solution of (S)-tert-butyl 2-amino-3-cyclohexylpropyl(methyl)carbamate (81 mg, 0.3 mmol), prepared using procedures described in U.S. Prov. App No. 05/036,230 (PCT App No. 60/616,770), and DIEA (161 mg, 1.25 mmol) in anhydrous CH2Cl2 (8 mL) followed by stirring for 1 h. The solution was added to methyl 2-(1-(3-chlorophenyl)-3-(methylamino)propoxy)ethylcarbamate (75 mg, 0.25 mmol) in anhydrous CH2Cl2 (4 mL). The reaction mixture was allowed to warm to room temperature and stirred overnight. After the reaction was completed, the solvent was removed in vacuo. The product was purified with preparative TLC to afford tert-butyl (S)-2-(3-(3-(2-(methoxycarbonylamino)ethoxy)-3-(3-chlorophenyl)propyl)-3-methylureido)-3-cyclohexylpropyl(methyl)carbamate (70 mg, 50%).

Workup

  1. customprepared
  2. stirringstirred overnight
  3. customthe solvent was removed in vacuo
  4. customThe product was purified with preparative TLC

Sources & evidence

ORD record
ord-bb1820f9a8324aaea13897e9d76d59b3
Source dataset
uspto-grants-2012_01
Patent number
US08106221B2

Reaction notes

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