1,3-Dibromopropane → HCID 69705675, compound

HRID 2183725Notes

Reaction equation

[CH2:1]([O:3][C:4](=[O:35])[CH:5]([NH:11][C:12]1[CH:13]=[N:14][C:15]([O:18][C:19]2[CH:20]=[C:21]3[C:25](=[CH:26][CH:27]=2)[N:24]([C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=2)[N:23]=[CH:22]3)=[CH:16][CH:17]=1)[C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH3:2].Br[CH2:37][CH2:38][CH2:39]Br.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O>[CH2:9]([O:8][C:6]([C:5]1([C:4]([O:3][CH2:1][CH3:2])=[O:35])[CH2:39][CH2:38][CH2:37][N:11]1[C:12]1[CH:13]=[N:14][C:15]([O:18][C:19]2[CH:20]=[C:21]3[C:25](=[CH:26][CH:27]=2)[N:24]([C:28]2[CH:29]=[CH:30][C:31]([F:34])=[CH:32][CH:33]=2)[N:23]=[CH:22]3)=[CH:16][CH:17]=1)=[O:7])[CH3:10]

Participants

Conditions

Temperature: 55 °C

Procedure

1-{6-[1-(4-Fluoro-phenyl)-1H-indazol-5-yloxy]-pyridin-3-yl}-pyrrolidine-2,2-dicarboxylic acid diethyl ester is prepared by dissolving 2-{6-[1-(4-Fluoro-phenyl)-1H-indazol-5-yloxy]-pyridin-3-ylamino}-malonic acid diethyl ester (9.25 mmol) in dimethylformamide (90 mL), followed by addition of 1,3 dibromopropane (938 μL, 9.25 mmol) and cesium carbonate (6 grams, 18.5 mmol). The reaction mixture is stirred for approximately 24 hours to 48 hours. The mixture is filtered through celite, and then concentrated under vacuum while heating to 55° C. to remove the dimethylformamide (azeotroping with toluene). The crude product obtained is chromatographed on silica gel (ISCO MPLC purification, 40 minutes, 0-50% ethyl acetate gradient, Biotage flash 40m column) to provide the title compound.

Workup

filtrationThe mixture is filtered through celite
concentrationconcentrated under vacuum
customto remove the dimethylformamide (azeotroping with toluene)
customThe crude product obtained

Sources & evidence

ORD record: ord-31fd04d74c494613a0405cc888dabdd7
Source dataset: uspto-grants-2005_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06900201B2

Reaction notes

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