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

HRID 506122Notes

Reaction equation

HRID 506122 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]([CH:20]3[CH2:23][CH2:22][CH2:21]3)[C:10]3[C:15]([C:16]=2[C:17]#[N:18])=[CH:14][CH:13]=[C:12]([OH:19])[CH:11]=3)=[CH:4][CH:3]=1.Cl[C:25]([O:27][C:28]1[CH:33]=[CH:32][C:31]([N+]([O-])=O)=C[CH:29]=1)=[O:26].C1(C(C)O)CC1>N1C=CC=CC=1.Cl>[CH:33]1([CH:28]([O:27][C:25](=[O:26])[NH:1][C:2]2[CH:7]=[CH:6][C:5]([C:8]3[N:9]([CH:20]4[CH2:21][CH2:22][CH2:23]4)[C:10]4[C:15]([C:16]=3[C:17]#[N:18])=[CH:14][CH:13]=[C:12]([OH:19])[CH:11]=4)=[CH:4][CH:3]=2)[CH3:29])[CH2:32][CH2:31]1

Participants

6

Reactant 3

HCID 791041-CyclopropylethanolHCID 821294-Nitrophenyl chloroformateHCID 497727192-(4-Aminophenyl)-1-cyclobutyl-6-hydroxy-indole-3-carbonitrile

Product 1

HCID 59425704[4-(3-cyano-1-cyclobutyl-6-hydroxy-1H-indol-2-yl)-phenyl]-carbamic acid 1-cyclopropyl-ethyl esterYield 80%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 1049PyridineSolvent

Procedure

To a solution of 2-(4-aminophenyl)-1-cyclobutyl-6-hydroxy-1H-indole-3-carbonitrile (909 mg, 3 mmol) in pyridine (5 mL) is added 4-nitrophenyl chloroformate (6 mmol) at room temperature and then stirred for 2 h at room temperature. To the reaction is added cyclopropyl methyl carbinol and then stirred for 8 h at 80° C. The reaction mixture is diluted with 1N HCl and then extracted with ethyl acetate. The organic layer is concentrated and the residue is dissolved in EtOAc and triturated with hexane. The precipitate is collected by filtration and washed with hexane and dried in vacuo to afford [4-(3-cyano-1-cyclobutyl-6-hydroxy-1H-indol-2-yl)-phenyl]-carbamic acid 1-cyclopropyl-ethyl ester (996 mg, 80%).

Workup

  1. stirringstirred for 8 h at 80° C
  2. extractionextracted with ethyl acetate
  3. concentrationThe organic layer is concentrated
  4. dissolutionthe residue is dissolved in EtOAc
  5. customtriturated with hexane
  6. filtrationThe precipitate is collected by filtration
  7. washwashed with hexane
  8. customdried in vacuo

Sources & evidence

ORD record
ord-eb58d5282d394488b120d0996ee1af01
Source dataset
uspto-grants-2010_08
Patent number
US07781478B2

Reaction notes

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