Lithium borohydride → 1-(4-chloro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic acid {1-[5-(3-hydroxy-propane-1-sulfonyl)-pyridin-3-yl]-butyl}-amide

HRID 2067978Notes

Reaction equation

HRID 2067978 reaction equation
C[O:2][C:3](=O)[CH2:4][CH2:5][S:6]([C:9]1[CH:10]=[N:11][CH:12]=[C:13]([CH:15]([NH:19][C:20]([C:22]2[CH:23]=[N:24][N:25]([C:28]3[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=3)[C:26]=2[CH3:27])=[O:21])[CH2:16][CH2:17][CH3:18])[CH:14]=1)(=[O:8])=[O:7].[BH4-].[Li+]>C1COCC1>[OH:2][CH2:3][CH2:4][CH2:5][S:6]([C:9]1[CH:14]=[C:13]([CH:15]([NH:19][C:20]([C:22]2[CH:23]=[N:24][N:25]([C:28]3[CH:29]=[CH:30][C:31]([Cl:34])=[CH:32][CH:33]=3)[C:26]=2[CH3:27])=[O:21])[CH2:16][CH2:17][CH3:18])[CH:12]=[N:11][CH:10]=1)(=[O:8])=[O:7]

Participants

4

Reactant 2

HCID 4148881Lithium borohydrideHCID 444808683-[5-(1-{[1-(4-chloro-phenyl)-5-methyl-1H-pyrazole-4-carbonyl]-amino}-butyl)-pyridine-3-sulfonyl]-propionic acid methyl ester

Product 1

HCID 444811091-(4-chloro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic acid {1-[5-(3-hydroxy-propane-1-sulfonyl)-pyridin-3-yl]-butyl}-amideYield 17%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

A solution of 3-[5-(1-{[1-(4-chloro-phenyl)-5-methyl-1H-pyrazole-4-carbonyl]-amino}-butyl)-pyridine-3-sulfonyl]-propionic acid methyl ester (51 mg, 0.10 mmol) in THF (2.5 mL) is treated lithium borohydride (13 mg, 0.59 mmol) and heated at 70° C. for 1 hour. After cooling to room temperature, the reaction is quenched by slow addition of 10 mL of water and extracted with EtOAc (2×25 mL). The combined organic layers are washed with brine (50 mL), dried over magnesium sulfate, filtered and concentrated in vacuo. Purification by flash chromatography on silica gel (eluted with 50 to 100% EtOAc/hexanes) followed by preparative reverse phase HPLC (eluted with 5 to 95% CH3CN/H2O and 0.1% TFA as additive) affords 1-(4-chloro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic acid {1-[5-(3-hydroxy-propane-1-sulfonyl)-pyridin-3-yl]-butyl}-amide (8.0 mg, 17%).

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe reaction is quenched by slow addition of 10 mL of water
  3. extractionextracted with EtOAc (2×25 mL)
  4. washThe combined organic layers are washed with brine (50 mL)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification by flash chromatography on silica gel (eluted with 50 to 100% EtOAc/hexanes)
  9. washfollowed by preparative reverse phase HPLC (eluted with 5 to 95% CH3CN/H2O and 0.1% TFA as additive)

Sources & evidence

ORD record
ord-ec39bd7d4364496797ebdc398c1bbe76
Source dataset
uspto-grants-2012_10
Patent number
US08293917B2

Reaction notes

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