Cesium carbonate → HCID 68282609, compound

HRID 513027Notes

Reaction equation

HRID 513027 reaction equation
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

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 162179852-Dicyclohexylphosphino-2',6'-diisopropoxybiphenylHCID 67330070(3R,5R)-5-(3-fluorophenyl)pyrrolidin-3-olHCID 68282460HCID 68282460, compound

Product 1

HCID 68282609HCID 68282609, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6386tert-ButanolSolvent

Conditions

Temperature
120 °C

Procedure

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)+

Workup

  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

Sources & evidence

ORD record
ord-e22dd26f7f2d47dab45fd853920507f7
Source dataset
uspto-grants-2015_08
Patent number
US09102671B2

Reaction notes

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