Cesium carbonate → HCID 117843598, compound

HRID 2209256Notes

Reaction equation

HRID 2209256 reaction equation
Br[C:2]1[CH:3]=[C:4]([O:13][C@@H:14]([C@@H:16]2[CH2:20][C:19](=[O:21])[N:18]([C@@H:22]([C:24]3[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=3)[CH3:23])[CH2:17]2)[CH3:15])[C:5]2[N:6]([N:8]=[CH:9][C:10]=2[C:11]#[N:12])[CH:7]=1.[C:32]([O:36][C:37]([N:39]1[CH2:44][CH2:43][N:42]([C:45]2[CH:50]=[CH:49][C:48](B(O)O)=[CH:47][CH:46]=2)[CH2:41][CH2:40]1)=[O:38])([CH3:35])([CH3:34])[CH3:33].C(=O)([O-])[O-].[Cs+].[Cs+].O1CCOCC1>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.O>[C:11]([C:10]1[CH:9]=[N:8][N:6]2[CH:7]=[C:2]([C:48]3[CH:47]=[CH:46][C:45]([N:42]4[CH2:41][CH2:40][N:39]([C:37]([O:36][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:38])[CH2:44][CH2:43]4)=[CH:50][CH:49]=3)[CH:3]=[C:4]([O:13][C@@H:14]([C@@H:16]3[CH2:20][C:19](=[O:21])[N:18]([C@@H:22]([C:24]4[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=4)[CH3:23])[CH2:17]3)[CH3:15])[C:5]=12)#[N:12]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 52330144-(4-BOC-Piperazino)phenylboronic acidHCID 117844058HCID 117844058, compound

Product 1

HCID 117843598HCID 117843598, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

To an appropriate sized microwave vial, 6-bromo-4-((R)-1-((R)-1-((R)-1-(4-methoxyphenyl)ethyl)-5-oxopyrrolidin-3-yl)ethoxy)pyrazolo[1,5-a]pyridine-3-carbonitrile (91.0 mg, 0.188 mmol), (4-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenyl)boronic acid (86.5 mg, 0.282 mmol), cesium carbonate (184 mg, 0.565 mmol), dioxane (2.0 mL) and water (0.5 mL) were added. The mixture was degassed with nitrogen for 10 minutes. Tetrakis(triphenylphosphine)palladium(0) catalyst (21.8 mg, 0.0188 mmol) was added and the solution was heated at 100° C. for 45 minutes. After cooling to room temperature, the reaction was concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (100% EtOAc) to afford tert-butyl 4-(4-(3-cyano-4-((R)-1-((R)-1-((R)-1-(4-methoxyphenyl)ethyl)-5-oxopyrrolidin-3-yl)ethoxy)pyrazolo[1,5-a]pyridin-6-yl)phenyl)piperazine-1-carboxylate.

Workup

  1. customThe mixture was degassed with nitrogen for 10 minutes
  2. temperatureAfter cooling to room temperature
  3. concentrationthe reaction was concentrated under reduced pressure
  4. customThe residue was purified by flash column chromatography on silica gel (100% EtOAc)

Sources & evidence

ORD record
ord-ed4071fd1962424d82047228e4bd7b53
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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