Dimethylformamide → HCID 22472971, compound

HRID 2183740Notes

Reaction equation

HRID 2183740 reaction equation
C(O[C:4]([C:6]1([C:28](OCC)=[O:29])[CH2:10][CH2:9][CH2:8][N:7]1[C:11]1[CH:12]=[N:13][C:14]([O:17][C:18]2[CH:19]=[C:20]3[C:24](=[CH:25][CH:26]=2)[N:23]([CH3:27])[N:22]=[CH:21]3)=[CH:15][CH:16]=1)=[O:5])C.C(OC(=O)C(NC1C=[N:46][C:47]([O:50]C2C=C3C(=CC=2)N(C)N=C3)=CC=1)C(OCC)=O)C.BrCCCBr.C(=O)([O-])[O-].[Cs+].[Cs+].C[N:74](C)C=O>>[CH3:27][N:23]1[C:24]2[C:20](=[CH:19][C:18]([O:17][C:14]3[N:13]=[CH:12][C:11]([N:7]4[C:6]5([C:28](=[O:29])[NH:74][C:47](=[O:50])[NH:46][C:4]5=[O:5])[CH2:10][CH2:9][CH2:8]4)=[CH:16][CH:15]=3)=[CH:26][CH:25]=2)[CH:21]=[N:22]1

Participants

6

Reactant 5

HCID 6228DimethylformamideHCID 80011,3-DibromopropaneHCID 10796Cesium carbonateHCID 69704432HCID 69704432, compoundHCID 69706160HCID 69706160, compound

Product 1

HCID 22472971HCID 22472971, compound

Conditions

Temperature
55 °C

Procedure

1-[6-(1-Methyl-1H-indazol-5-yloxy)-pyridin-3-yl]-pyrrolidine-2,2-dicarboxylic acid diethyl ester can be prepared by dissolving 2-[6-(Methyl-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

  1. filtrationThe mixture is filtered through celite
  2. concentrationconcentrated under vacuum
  3. customto remove the dimethylformamide (azeotroping with toluene)
  4. customThe crude product obtained
  5. customis chromatographed on silica gel (ISCO MPLC purification, 40 minutes, 0-50% ethyl acetate gradient, Biotage flash 40m column)

Sources & evidence

ORD record
ord-284a58f428364097bbd5fbd2fc7c6274
Source dataset
uspto-grants-2005_05
Patent number
US06900201B2

Reaction notes

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