Toluene → {4-[6-(2-chloroethoxy)-3-cyano-1-cyclobutyl-1H-indol-2-yl]-phenyl}-carbamic acid 1-cyclopropyl-ethyl ester

HRID 502267Notes

Reaction equation

HRID 502267 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]([CH:23]3[CH2:26][CH2:25][CH2:24]3)[C:10]3[C:15]([C:16]=2[C:17]#[N:18])=[CH:14][CH:13]=[C:12]([O:19][CH2:20][CH2:21][Cl:22])[CH:11]=3)=[CH:4][CH:3]=1.C1(C)C=CC=CC=1.[CH:34]1([C@H:37]([OH:39])[CH3:38])[CH2:36][CH2:35]1.[C:40](Cl)(Cl)=[O:41]>ClCCCl.CN(C1C=CN=CC=1)C.Cl>[CH:34]1([CH:37]([O:39][C:40](=[O:41])[NH:1][C:2]2[CH:7]=[CH:6][C:5]([C:8]3[N:9]([CH:23]4[CH2:26][CH2:25][CH2:24]4)[C:10]4[C:15]([C:16]=3[C:17]#[N:18])=[CH:14][CH:13]=[C:12]([O:19][CH2:20][CH2:21][Cl:22])[CH:11]=4)=[CH:4][CH:3]=2)[CH3:38])[CH2:36][CH2:35]1

Participants

8

Reactant 4

HCID 1140TolueneHCID 6371PhosgeneHCID 6999829(1R)-1-cyclopropylethan-1-olHCID 594250482-(4-Amino-phenyl)-6-(2-chloro-ethoxy)-1-cyclobutyl-1H-indole-3-carbonitrile

Product 1

HCID 59426250{4-[6-(2-chloroethoxy)-3-cyano-1-cyclobutyl-1H-indol-2-yl]-phenyl}-carbamic acid 1-cyclopropyl-ethyl esterYield 77%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 111,2-DichloroethaneSolventHCID 313Hydrochloric AcidSolvent

Conditions

Temperature
80 °C

Procedure

2-(4-Amino-phenyl)-6-(2-chloro-ethoxy)-1-cyclobutyl-1H-indole-3-carbonitrile (800 mg, 2.19 mmol) was dissolved in phosgene in toluene (2M, 10 mL, 5.00 mmol) and stirred for 2 h at 80° C. in a sealed tube. Solvent was removed and the white solid obtained was suspended in 1 ml of DCE. To this solution was added (R)-1-cyclopropylethanol (400 uL, 5.28 mmol) and DMAP (268 mg, 2.19 mmol). Solution was stirred in a sealed tube for 16 h at room temperature. An aqueous workup was performed in 0.5M HCl (200 mL) and extracted with EtOAc (2×100 mL). The organic layers were combined, dried over MgSO4 and concentrated. Solid product was triturated with ether to generate 800 mg (77% yield) of {4-[6-(2-Chloro-ethoxy)-3-cyano-1-cyclobutyl-1H-indol-2-yl]-phenyl}-carbamic acid 1-cyclopropyl-ethyl ester, as a white solid.

Workup

  1. customSolvent was removed
  2. customthe white solid obtained
  3. stirringSolution was stirred in a sealed tube for 16 h at room temperature
  4. extractionextracted with EtOAc (2×100 mL)
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customSolid product was triturated with ether

Sources & evidence

ORD record
ord-99e908874dd84d09936dc52d77ea64c5
Source dataset
uspto-grants-2010_08
Patent number
US07772271B2

Reaction notes

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