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 2067978ノート

反応式

HRID 2067978 の反応式
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]

参加物

4

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
70 °C

実験手順

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%).

後処理

  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)

出典と根拠

ORDレコード
ord-ec39bd7d4364496797ebdc398c1bbe76
出典データセット
uspto-grants-2012_10
特許番号
US08293917B2

反応ノート

読み込み中…