Dimethylformamide → HCID 86642828, compound

HRID 1667718Notes

Reaction equation

HRID 1667718 reaction equation
[NH2:1][C:2]1[S:3][C:4]([C:14]([NH2:16])=[O:15])=[C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[C:9]([Cl:13])[CH:8]=2)[N:6]=1.[C:17]([O:21][C:22]([N:24]1[CH2:29][CH2:28][CH:27]([O:30][C:31]2[CH:36]=[CH:35][C:34]([N+:37]([O-:39])=[O:38])=[C:33](F)[CH:32]=2)[CH2:26][CH2:25]1)=[O:23])([CH3:20])([CH3:19])[CH3:18].CN(C)C=O.C(=O)([O-])[O-].[Cs+].[Cs+]>C(OCC)(=O)C.O>[C:17]([O:21][C:22]([N:24]1[CH2:29][CH2:28][CH:27]([O:30][C:31]2[CH:32]=[CH:33][C:34]([N+:37]([O-:39])=[O:38])=[C:35]([NH:1][C:2]3[S:3][C:4]([C:14](=[O:15])[NH2:16])=[C:5]([C:7]4[CH:12]=[CH:11][CH:10]=[C:9]([Cl:13])[CH:8]=4)[N:6]=3)[CH:36]=2)[CH2:26][CH2:25]1)=[O:23])([CH3:20])([CH3:18])[CH3:19]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 166588232-Amino-4-(3-chlorophenyl)thiazole-5-carboxamideHCID 67427269HCID 67427269, compound

Product 1

HCID 86642828HCID 86642828, compoundYield 46.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of 0.35 g (1.38 mmole) of 2-amino-4-(3-chloro-phenyl)-thiazole-5-carboxylic acid amide (V.2), 0.56 g (1.66 mmole) of 4-(3-fluoro-4-nitro-phenoxy)-piperidine-1-carboxylic acid tert-butyl ester (IV.21a) and 10 mL of dimethylformamide was added 2.24 g (6.90 mmole) of cesium carbonate. The mixture was heated at 70 degrees for 5 hours and then diluted with ethyl acetate and water. The aqueous phase was extracted three times with ethyl acetate. The combined organic layers were washed with water and brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with ethyl acetate-hexanes (gradient 0:100-40:60) to give 0.37 g of 4-{3-[5-carbamoyl-4-(3-chloro-phenyl)-thiazole-2-ylamino]-4-nitro-phenoxy}-piperidine-1-carboxylic acid tert-butyl ester (VI.21).

Workup

  1. temperatureThe mixture was heated at 70 degrees for 5 hours
  2. extractionThe aqueous phase was extracted three times with ethyl acetate
  3. washThe combined organic layers were washed with water and brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel chromatography
  8. washeluting with ethyl acetate-hexanes (gradient 0:100-40:60)

Sources & evidence

ORD record
ord-306b4319ac7b4f218ed014fbe2074bf4
Source dataset
uspto-grants-2011_10
Patent number
US08044213B2

Reaction notes

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