Pyridine → (R)-[4-(3-cyano-1-cyclobutyl-6-methanesulfonylmethoxy-1H-indol-2-yl)-phenyl]-carbamic acid 1-cyclopropyl-ethyl ester

HRID 502282Notes

Reaction equation

HRID 502282 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]([CH:25]3[CH2:28][CH2:27][CH2:26]3)[C:10]3[C:15]([C:16]=2[C:17]#[N:18])=[CH:14][CH:13]=[C:12]([O:19][CH2:20][S:21]([CH3:24])(=[O:23])=[O:22])[CH:11]=3)=[CH:4][CH:3]=1.Cl[C:30]([O:32][C:33]1[CH:38]=[CH:37][C:36]([N+]([O-])=O)=C[CH:34]=1)=[O:31].N1C=CC=CC=1.C1([C@H](O)C)CC1>C(Cl)Cl.ClCCCl>[CH:38]1([C@H:33]([O:32][C:30](=[O:31])[NH:1][C:2]2[CH:3]=[CH:4][C:5]([C:8]3[N:9]([CH:25]4[CH2:28][CH2:27][CH2:26]4)[C:10]4[C:15]([C:16]=3[C:17]#[N:18])=[CH:14][CH:13]=[C:12]([O:19][CH2:20][S:21]([CH3:24])(=[O:23])=[O:22])[CH:11]=4)=[CH:6][CH:7]=2)[CH3:34])[CH2:37][CH2:36]1

Participants

7

Reactant 4

HCID 1049PyridineHCID 821294-Nitrophenyl chloroformateHCID 6999829(1R)-1-cyclopropylethan-1-olHCID 684271882-(4-amino-phenyl)-1-cyclobutyl-6-methanesulfonylmethoxy-1H-indole-3-carbonitrile

Product 1

HCID 59606420(R)-[4-(3-cyano-1-cyclobutyl-6-methanesulfonylmethoxy-1H-indol-2-yl)-phenyl]-carbamic acid 1-cyclopropyl-ethyl esterYield 83%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

2-(4-Amino-phenyl)-1-cyclobutyl-6-methanesulfonylmethoxy-1H-indole-3-carbonitrile (100 mg, 0.25 mmol) was combined with p-nitrophenyl chloroformate (120 mg, 0.6 mmol), DCE (1 mL), and pyridine (60 μL, 0.75 mmol) and stirred at room temperature for 1 h. To this mixture was added (R)-1-Cyclopropylethanol (90 μL, 0.92 mmol) and then heated at 80° C. for 2 h. The reaction mixture was diluted with CH2Cl2 and washed with dilute aqueous NaOH solution. The organic layer was dried, concentrated and purified by silica gel chromatography (95:5 CH2Cl2/EtOAc) to provide (R)-[4-(3-cyano-1-cyclobutyl-6-methanesulfonylmethoxy-1H-indol-2-yl)-phenyl]-carbamic acid 1-cyclopropyl-ethyl ester (105 mg, 83%) as a white solid.

Workup

  1. temperatureheated at 80° C. for 2 h
  2. washwashed with dilute aqueous NaOH solution
  3. customThe organic layer was dried
  4. concentrationconcentrated
  5. custompurified by silica gel chromatography (95:5 CH2Cl2/EtOAc)

Sources & evidence

ORD record
ord-53d60dd15c8643219c15e18f618871fa
Source dataset
uspto-grants-2010_08
Patent number
US07772271B2

Reaction notes

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