Cesium carbonate → 5-((2R,4R)-2-(3-fluorophenyl)-4-hydroxypyrrolidin-1-yl)-N,N-bis(4-methoxybenzyl)pyrazolo[1,5-a]pyridine-3-carboxamide

HRID 513027ノート

反応式

HRID 513027 の反応式
Br[C:2]1[CH:7]=[CH:6][N:5]2[N:8]=[CH:9][C:10]([C:11]([N:13]([CH2:23][C:24]3[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=3)[CH2:14][C:15]3[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=3)=[O:12])=[C:4]2[CH:3]=1.CC(OC1C=CC=C(OC(C)C)C=1C1C(P(C2CCCCC2)C2CCCCC2)=CC=CC=1)C.C(=O)([O-])[O-].[Cs+].[Cs+].[F:71][C:72]1[CH:73]=[C:74]([C@@H:78]2[NH:82][CH2:81][C@H:80]([OH:83])[CH2:79]2)[CH:75]=[CH:76][CH:77]=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CC(O)(C)C>[F:71][C:72]1[CH:73]=[C:74]([C@H:78]2[CH2:79][C@@H:80]([OH:83])[CH2:81][N:82]2[C:2]2[CH:7]=[CH:6][N:5]3[N:8]=[CH:9][C:10]([C:11]([N:13]([CH2:23][C:24]4[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=4)[CH2:14][C:15]4[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=4)=[O:12])=[C:4]3[CH:3]=2)[CH:75]=[CH:76][CH:77]=1

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 162179852-Dicyclohexylphosphino-2',6'-diisopropoxybiphenylHCID 67330070(3R,5R)-5-(3-fluorophenyl)pyrrolidin-3-olHCID 682824605-bromo-N,N-bis(4-methoxybenzyl)pyrazolo[1,5-a]pyridine-3-carboxamide

生成物 1

HCID 682826095-((2R,4R)-2-(3-fluorophenyl)-4-hydroxypyrrolidin-1-yl)-N,N-bis(4-methoxybenzyl)pyrazolo[1,5-a]pyridine-3-carboxamide

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 6386tert-Butanol溶媒

反応条件

温度
120 °C

実験手順

A N2 purged flask was charged with 5-bromo-N,N-bis(4-methoxybenzyl)pyrazolo[1,5-a]pyridine-3-carboxamide (I-26) (0.19 g, 0.39 mmol), palladium acetate (3 mg, 12 μmol), RuPhos (11 mg, 24 μmol), cesium carbonate (0.25 g, 0.78 mmol), tBuOH (1 mL) and (3R,5R)-5-(3-fluorophenyl)pyrrolidin-3-ol (I-32) (71 mg, 0.39 mmol). The contents were heated to 120° C. overnight in an oil bath. Upon cooling to room temperature the reaction was filtered through celite and concentrated. The crude product was purified by column chromatography on silica gel with EtOAc/hexanes gradient as eluant to yield 5-((2R,4R)-2-(3-fluorophenyl)-4-hydroxypyrrolidin-1-yl)-N,N-bis(4-methoxybenzyl)pyrazolo[1,5-a]pyridine-3-carboxamide (I-33). 1H NMR (400 MHz, CDCl3) δ 7.96-7.84 (m, 1 H), 7.65-7.49 (m, 1 H), 7.09-7.04 (m, 3 H), 7.01-6.95 (m, 3 H), 6.92-6.81 (m, 3 H), 6.72-6.64 (m, 4 H), 6.05-5.92 (m, 1 H), 4.79-4.69 (m, 1 H), 4.56-4.41 (m, 3 H), 4.38-4.26 (m, 2 H), 3.96-3.86 (m, 1 H), 3.66-3.59 (m, 6 H), 2.63-2.49 (m, 1 H), 2.06-1.94 (m, 1 H), 1.87-1.79 (m, 1 H). MS m/z 581.2 (M+1)+

後処理

  1. temperatureUpon cooling to room temperature the reaction
  2. filtrationwas filtered through celite
  3. concentrationconcentrated
  4. 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-e22dd26f7f2d47dab45fd853920507f7
出典データセット
uspto-grants-2015_08
特許番号
US09102671B2

反応ノート

読み込み中…