1-Bromo-3-chloropropane → HCID 59425206, compound

HRID 506123Notes

Reaction equation

[C:1]([C:3]1[C:11]2[C:6](=[CH:7][C:8]([OH:12])=[CH:9][CH:10]=2)[N:5]([CH:13]2[CH2:16][CH2:15][CH2:14]2)[C:4]=1[C:17]1[CH:22]=[CH:21][C:20]([NH:23][C:24]([NH:26][CH:27]([CH3:29])[CH3:28])=[O:25])=[CH:19][CH:18]=1)#[N:2].C([O-])([O-])=O.[K+].[K+].Br[CH2:37][CH2:38][CH2:39][Cl:40]>C(#N)C>[Cl:40][CH2:39][CH2:38][CH2:37][O:12][C:8]1[CH:7]=[C:6]2[C:11]([C:3]([C:1]#[N:2])=[C:4]([C:17]3[CH:18]=[CH:19][C:20]([NH:23][C:24]([NH:26][CH:27]([CH3:29])[CH3:28])=[O:25])=[CH:21][CH:22]=3)[N:5]2[CH:13]2[CH2:14][CH2:15][CH2:16]2)=[CH:10][CH:9]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 1-[4-(3-cyano-1-cyclobutyl-6-hydroxy-1H-indol-2-yl)-phenyl]-3-isopropyl-urea (750 mg, 1.93 mmol) in 10 mL of acetonitrile is added anhydrous K2CO3 (800 mg, 5.79 mmol) and 1-bromo-3-chloropropane (382 μL, 3.86 mmol). After stirring overnight at 80° C., the reaction mixture is cooled and solvent is removed. The reaction is re-suspended in 100 mL of ethyl acetate. The organic phase is washed with 200 mL of H2O, and the aqueous phase is re-extracted 2× with 100 mL of ethyl acetate. The organic phases are combined, dried over MgSO4 and the solvent is removed to afford 769 mg (86%) of 1-{4-[6-(3-chloropropoxy)-3-cyano-1-cyclobutyl-1H-indol-2-yl]-phenyl}-3-isopropyl-urea as a tan powder.

Workup

temperaturethe reaction mixture is cooled
customsolvent is removed
washThe organic phase is washed with 200 mL of H2O
extractionthe aqueous phase is re-extracted 2× with 100 mL of ethyl acetate
dry with materialdried over MgSO4
customthe solvent is removed

Sources & evidence

ORD record: ord-5585d809c8ab4a619924b7a1c978a7ea
Source dataset: uspto-grants-2010_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07781478B2

Reaction notes

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