Pyridine → HCID 68618357, compound

HRID 1433801Notes

Reaction equation

HRID 1433801 reaction equation
[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([NH:18][C@@H:19]([CH:23]([CH3:25])[CH3:24])[C:20]([OH:22])=O)=[O:17])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.C(Cl)(=O)C(Cl)=O.[NH2:32][C:33]1[CH:40]=[CH:39][C:36]([C:37]#[N:38])=[CH:35][C:34]=1[F:41].N1C=CC=CC=1>CN(C)C=O.ClCCl.CN(C)C1C=CN=CC=1>[CH:10]1[C:11]2[CH:12]([CH2:14][O:15][C:16](=[O:17])[NH:18][C@H:19]([C:20](=[O:22])[NH:32][C:33]3[CH:40]=[CH:39][C:36]([C:37]#[N:38])=[CH:35][C:34]=3[F:41])[CH:23]([CH3:24])[CH3:25])[C:13]3[C:5](=[CH:4][CH:3]=[CH:2][CH:1]=3)[C:6]=2[CH:7]=[CH:8][CH:9]=1

Participants

8

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 688217FMOC-L-valineHCID 27564314-Amino-3-fluorobenzonitrile

Product 1

HCID 68618357HCID 68618357, compoundYield 77%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-methyl-butyric acid (2.5 g, 7.37 mmol) and a few drops of N,N-dimethylformamide in dichloromethane (20 mL) was slowly added oxalyl chloride (1.3 mL, 14.74 mmol) at 0° C. under an atmosphere of dry nitrogen. The mixture was stirred for 15 minutes at 0° C. and 2 hours at room temperature. After removal of the solvent, the residue was dissolved in dichloromethane (20 mL) and to the resulting solution was added 4-amino-3-fluoro-benzonitrile (840 mg, 6.14 mmol), 4-dimethylaminopyridine (150 mg, 1.2 mmol) and pyridine (0.78 mL, 9.21 mmol) at 0° C. The mixture was stirred for 2 hrs at 0° C. and overnight at room temperature. The reaction was quenched with 1 M aqueous citric acid solution and then extracted with dichloromethane (three times). The combined organic extracts were washed with 1 M aqueous citric acid solution, brine, saturated aqueous sodium carbonate, brine, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by chromatography over silica gel gradient eluted from 100% dichloromethane up to 10% methanol/90% dichloromethane over 30 minutes. Concentration of the product containing fractions gave [(S)-1-(4-cyano-2-fluoro-phenylcarbamoyl)-2-methyl-propyl]-carbamic acid 9H-fluoren-9-ylmethyl ester as a white solid (2.15 mg, 77%).

Workup

  1. customat 0° C.
  2. customAfter removal of the solvent
  3. dissolutionthe residue was dissolved in dichloromethane (20 mL) and to the resulting solution
  4. stirringThe mixture was stirred for 2 hrs at 0° C. and overnight at room temperature
  5. customThe reaction was quenched with 1 M aqueous citric acid solution
  6. extractionextracted with dichloromethane (three times)
  7. washThe combined organic extracts were washed with 1 M aqueous citric acid solution, brine, saturated aqueous sodium carbonate, brine
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by chromatography over silica gel gradient
  12. washeluted from 100% dichloromethane up to 10% methanol/90% dichloromethane over 30 minutes
  13. additionConcentration of the product containing fractions

Sources & evidence

ORD record
ord-7156e2b66b634c119d8d70d8c4342d91
Source dataset
uspto-grants-2009_11
Patent number
US07612212B2

Reaction notes

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