4-Methylpyrazole → 4-[3'-Fluoro-5'-(4-methyl-pyrazol-1-ylmethyl)-2,3,5,6-tetrahydro-[1,2]bipyridinyl-4-ylideneaminooxy]-piperidine-1-carboxylic acid isopropyl ester

HRID 2066865Notes

Reaction equation

HRID 2066865 reaction equation
S(Cl)(C)(=O)=O.[CH:6]([O:9][C:10]([N:12]1[CH2:17][CH2:16][CH:15]([O:18][N:19]=[C:20]2[CH2:25][CH2:24][N:23]([C:26]3[C:31]([F:32])=[CH:30][C:29]([CH2:33]O)=[CH:28][N:27]=3)[CH2:22][CH2:21]2)[CH2:14][CH2:13]1)=[O:11])([CH3:8])[CH3:7].C(N(CC)CC)C.[CH3:42][C:43]1[CH:44]=[N:45][NH:46][CH:47]=1.[H-].[Na+]>C(Cl)Cl.CN(C=O)C.O>[CH:6]([O:9][C:10]([N:12]1[CH2:13][CH2:14][CH:15]([O:18][N:19]=[C:20]2[CH2:25][CH2:24][N:23]([C:26]3[C:31]([F:32])=[CH:30][C:29]([CH2:33][N:45]4[CH:44]=[C:43]([CH3:42])[CH:47]=[N:46]4)=[CH:28][N:27]=3)[CH2:22][CH2:21]2)[CH2:16][CH2:17]1)=[O:11])([CH3:7])[CH3:8]

Participants

9

Reactant 5

HCID 34064-MethylpyrazoleHCID 8471TriethylamineHCID 24758Sodium hydrideHCID 31297Methanesulfonyl chlorideHCID 583336054-(3'-Fluoro-5'-hydroxymethyl-2,3,5,6-tetrahydro-[1,2']bipyridinyl-4-ylideneaminooxy)-piperidine-1-carboxylic acid isopropyl ester

Product 1

HCID 583336124-[3'-Fluoro-5'-(4-methyl-pyrazol-1-ylmethyl)-2,3,5,6-tetrahydro-[1,2]bipyridinyl-4-ylideneaminooxy]-piperidine-1-carboxylic acid isopropyl ester

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
100 °C

Procedure

Mesyl chloride (96 μL, 1.2 mmol) was added to an ice cooled solution of 53-1 (0.25 g, 0.62 mmol) and triethylamine (0.26 mL, 1.9 mmol) in 5 mL of DCM. After 2 h, the mixture was diluted with DCM (30 mL), washed with brine (15 mL) and water (15 mL), dried and concentrated under vacuum. The residue was taken up in DMF and added to a mixture of 4-methyl-1H-pyrazole (0.8 mmol) and sodium hydride (30 mg, 60%, 0.8 mmol) in DMF which had been pre-stirred for 5 minutes. The mixture was heated to 100° C. for 2 h then allowed to cool down to room temperature, diluted with water (1.5 mL) and extracted with DCM (2 mL). The organic layer was concentrated under a stream of nitrogen, the residue was taken up in methanol and the mixture was purified by HPLC to afford 54-1: LC-MS 473.2 (MH+).

Workup

  1. washwashed with brine (15 mL) and water (15 mL)
  2. customdried
  3. concentrationconcentrated under vacuum
  4. temperatureto cool down to room temperature
  5. extractionextracted with DCM (2 mL)
  6. concentrationThe organic layer was concentrated under a stream of nitrogen
  7. customthe mixture was purified by HPLC
  8. customto afford 54-1

Sources & evidence

ORD record
ord-bd6c55ddffea460dadea2a5b42441102
Source dataset
uspto-grants-2012_10
Patent number
US08293729B2

Reaction notes

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