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 513027노트

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HRID 513027 반응식
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

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 6386tert-Butanol용매

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온도
120 °C

실험 절차

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)+

후처리

  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

출처 및 근거

ORD 기록
ord-e22dd26f7f2d47dab45fd853920507f7
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09102671B2

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