Cesium carbonate → ethyl 5-((2R,4S)-4-fluoro-2-(3-fluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyridine-3-carboxylate

HRID 513041

反応式

HRID 513041 の反応式
Br[C:2]1[CH:7]=[CH:6][N:5]2[N:8]=[CH:9][C:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[C:4]2[CH:3]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+].[F:64][C@@H:65]1[CH2:69][NH:68][C@@H:67]([C:70]2[CH:75]=[CH:74][CH:73]=[C:72]([F:76])[CH:71]=2)[CH2:66]1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[F:64][C@@H:65]1[CH2:69][N:68]([C:2]2[CH:7]=[CH:6][N:5]3[N:8]=[CH:9][C:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[C:4]3[CH:3]=2)[C@@H:67]([C:70]2[CH:75]=[CH:74][CH:73]=[C:72]([F:76])[CH:71]=2)[CH2:66]1

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 53249841Ethyl 5-bromopyrazolo[1,5-a]pyridine-3-carboxylateHCID 66684522(2R,4S)-4-fluoro-2-(3-fluorophenyl)pyrrolidine

生成物 1

HCID 60165028ethyl 5-((2R,4S)-4-fluoro-2-(3-fluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyridine-3-carboxylate

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
120 °C

実験手順

A N2 purged flask was charged with ethyl 5-bromopyrazolo[1,5-a]pyridine-3-carboxylate (27 mg, 0.1 mmol), tris(dibenzylideneacetone)dipalladium(0) (2 mg, 2 μmol), xantphos (5 mg, 8 μmol), cesium carbonate (46 mg, 0.14 mmol), 1,4-dioxane (0.5 mL) and (2R,4S)-4-fluoro-2-(3-fluorophenyl)pyrrolidine (I-6) (18 mg, 0.1 mmol). The contents were heated to 120° C. for 12 hours. Upon cooling to room temperature the reaction was partitioned with EtOAc and water. The organic layer was washed with water, brine, dried over magnesium sulfate, filtered and reduced to dryness. The crude product was purified by column chromatography on silica gel with EtOAc/hexanes gradient as eluant to yield ethyl 5-((2R,4S)-4-fluoro-2-(3-fluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyridine-3-carboxylate (X-1). 1H NMR (400 MHz, CDCl3) δ 8.20 (s, 1 H), 8.16 (d, J=7.6 Hz, 1 H), 7.31 (td, J=5.6, 7.6 Hz, 1 H), 7.05 (d, J=7.6 Hz, 1 H), 6.98 (d, J=2.8 Hz, 1 H), 6.96-6.91 (m, 2 H), 6.24 (dd, J=2.8, 8.0 Hz, 1 H), 5.39 (d, J=52.8 Hz, 1 H), 5.04 (dd, J=7.2, 9.2 Hz, 1H), 4.34-4.26 (m, 2 H), 4.17-3.90 (m, 2 H), 2.93-2.81 (m, 1 H), 2.11 (dddd, J=3.6, 9.2, 13.2, 40.8 Hz, 1 H). MS m/z 372.1 (M+1)+.

後処理

  1. temperatureUpon cooling to room temperature the reaction
  2. customwas partitioned with EtOAc and water
  3. washThe organic layer was washed with water, brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. customThe crude product was purified by column chromatography on silica gel with EtOAc/hexanes gradient as eluant

出典と根拠

ORDレコード
ord-cd37d316d9d8428d95597e21b332dd68
出典データセット
uspto-grants-2015_08
特許番号
US09102671B2

関連ノート

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