Ethyl Acetate → 3-(1-(2,4-difluorophenyl)-7-ethyl-6-oxo-6,7-dihydro-1H-pyrazolo[4,3-b]pyrazin-5-yl)-5-fluoro-4-methylbenzoic acid

HRID 383572

反応式

HRID 383572 の反応式
B([C:4]1[CH:5]=[C:6]([CH:10]=[C:11]([F:14])[C:12]=1[CH3:13])[C:7]([OH:9])=[O:8])(O)O.Cl[C:16]1[C:17](=[O:35])[N:18]([CH2:33][CH3:34])[C:19]2[N:24]([C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:26]=3[F:32])[N:23]=[CH:22][C:20]=2[N:21]=1.CCOC(C)=O>O1CCOCC1.C(=O)([O-])[O-].[Na+].[Na+].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:32][C:26]1[CH:27]=[C:28]([F:31])[CH:29]=[CH:30][C:25]=1[N:24]1[C:19]2[N:18]([CH2:33][CH3:34])[C:17](=[O:35])[C:16]([C:4]3[CH:5]=[C:6]([CH:10]=[C:11]([F:14])[C:12]=3[CH3:13])[C:7]([OH:9])=[O:8])=[N:21][C:20]=2[CH:22]=[N:23]1

参加物

7

反応物 3

HCID 8857Ethyl AcetateHCID 671973465-chloro-1-(2,4-difluorophenyl)-7-ethyl-1H-pyrazolo[4,3-b]pyrazin-6(7H)-oneHCID 671989493-Borono-5-fluoro-4-methylbenzoic acid

生成物 1

HCID 671996043-(1-(2,4-difluorophenyl)-7-ethyl-6-oxo-6,7-dihydro-1H-pyrazolo[4,3-b]pyrazin-5-yl)-5-fluoro-4-methylbenzoic acid

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 10340Sodium Carbonate溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
130 °C

実験手順

A mixture of tetrakis(triphenylphosphine)palladium(0) (28 mg, 24 μmol), 3-borono-5-fluoro-4-methylbenzoic acid (175 mg, 0.88 mmol) and 5-chloro-1-(2,4-difluorophenyl)-7-ethyl-1H-pyrazolo[4,3-b]pyrazin-6(7H)-one (250 mg, 0.80 mmol) in 4.0 mL dioxane and 2.0 mL of 1 N sodium carbonate was heated in a microwave at 130° C. for 30 min. The reaction mixture was treated with EtOAc (15 mL) and extracted with 1N NaOH (3×10 mL). The aqueous extracts were treated with 5 N HCl to pH 2 and extracted with DCM (3×15 mL). The combined DCM layers were dried over MgSO4, filtered and concentrated affording 3-(1-(2,4-difluorophenyl)-7-ethyl-6-oxo-6,7-dihydro-1H-pyrazolo[4,3-b]pyrazin-5-yl)-5-fluoro-4-methylbenzoic acid as a light orange-brown viscous oil. This material was used without purification. MS (ES+): 429.1 (M+H)+.

後処理

  1. extractionextracted with 1N NaOH (3×10 mL)
  2. additionThe aqueous extracts were treated with 5 N HCl to pH 2
  3. extractionextracted with DCM (3×15 mL)
  4. dry with materialThe combined DCM layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated

出典と根拠

ORDレコード
ord-0543c08ef74042e6a3ad6d8a7cb601c8
出典データセット
uspto-grants-2013_02
特許番号
US08367671B2

関連ノート

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