1-Chloroethyl chloroformate → HCID 66754702, compound

HRID 1631993Notes

Reaction equation

HRID 1631993 reaction equation
ClC(OC(Cl)C)=O.C([N:15]1[CH2:20][CH2:19][N:18]([C@@H:21]2[CH2:25][CH2:24][N:23]([C:26](=[O:56])[CH:27]([N:34]3[C:38]4[CH:39]=[C:40]([Cl:43])[CH:41]=[CH:42][C:37]=4[N:36]([S:44]([C:47]4[CH:52]=[CH:51][C:50]([O:53][CH3:54])=[CH:49][CH:48]=4)(=[O:46])=[O:45])[C:35]3=[O:55])[C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH2:22]2)[CH2:17][CH2:16]1)C1C=CC=CC=1>ClCCl>[Cl:43][C:40]1[CH:41]=[CH:42][C:37]2[N:36]([S:44]([C:47]3[CH:48]=[CH:49][C:50]([O:53][CH3:54])=[CH:51][CH:52]=3)(=[O:46])=[O:45])[C:35](=[O:55])[N:34]([CH:27]([C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=3)[C:26](=[O:56])[N:23]3[CH2:24][CH2:25][C@@H:21]([N:18]4[CH2:17][CH2:16][NH:15][CH2:20][CH2:19]4)[CH2:22]3)[C:38]=2[CH:39]=1

Participants

4

Reactant 2

HCID 5213051-Chloroethyl chloroformateHCID 66754714HCID 66754714, compound

Product 1

HCID 66754702HCID 66754702, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

118 mg (0.82 mmol) of 1-chloroethyl chloroformate were added to a solution of 550 mg (0.79 mmol) of 3-{2-[(R)-3-(4-benzylpiperazin-1-yl)-pyrrolidin-1-yl]-2-oxo-1-phenylethyl}-5-chloro-1-(4-methoxybenzenesulfonyl)-1,3-dihydrobenzimidazol-2-one (Example 142) in 5 ml dry dichloromethane while stirring at 0° C. The reaction mixture was subsequently stirred at 0° C. for 1 h and then at room temperature overnight. The solvent was removed in vacuo, and the residue was dissolved in 20 ml of methanol. The methanolic solution was stirred at 60° C. for 1 h and then concentrated under reduced pressure. The residue was dissolved in dichloromethane, mixed with 3 eq. of MP-carbonate (Argonaut, 1.69 mmol/g) and stirred at room temperature for 2 h. The solid phase reagent was filtered off and washed with dichloromethane. The filtrate was concentrated under reduced pressure and dried in vacuo. The residue was purified by chromatography on silica gel (mobile phase gradient 4-7% 1N ammoniacal methanol in dichloromethane) or by HPLC as described above. Yield: 231 mg (48%) of colorless solid

Workup

  1. stirringThe reaction mixture was subsequently stirred at 0° C. for 1 h
  2. customat room temperature
  3. customovernight
  4. customThe solvent was removed in vacuo
  5. dissolutionthe residue was dissolved in 20 ml of methanol
  6. stirringThe methanolic solution was stirred at 60° C. for 1 h
  7. concentrationconcentrated under reduced pressure
  8. dissolutionThe residue was dissolved in dichloromethane
  9. additionmixed with 3 eq. of MP-carbonate (Argonaut, 1.69 mmol/g)
  10. stirringstirred at room temperature for 2 h
  11. filtrationThe solid phase reagent was filtered off
  12. washwashed with dichloromethane
  13. concentrationThe filtrate was concentrated under reduced pressure
  14. customdried in vacuo
  15. customThe residue was purified by chromatography on silica gel (mobile phase gradient 4-7% 1N ammoniacal methanol in dichloromethane) or by HPLC

Sources & evidence

ORD record
ord-721037d44df8481c9b3d27ae016c711f
Source dataset
uspto-grants-2014_07
Patent number
US08791148B2

Reaction notes

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