Cesium carbonate → HCID 117842929, compound

HRID 2209244Notes

Reaction equation

HRID 2209244 reaction equation
Br[C:2]1[CH:3]=[C:4]([O:12][C@@H:13]([C@H:15]2[CH2:19][N:18]([C@@H:20]([C:22]3[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=3)[CH3:21])[C:17](=[O:30])[CH2:16]2)[CH3:14])[C:5]2[N:6]([N:8]=[CH:9][C:10]=2[Cl:11])[CH:7]=1.[C:31]([O:35][C:36]([N:38]1[CH2:43][CH2:42][N:41]([C:44]2[CH:49]=[CH:48][C:47](B(O)O)=[CH:46][CH:45]=2)[CH2:40][CH2:39]1)=[O:37])([CH3:34])([CH3:33])[CH3:32].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>[Cl:11][C:10]1[CH:9]=[N:8][N:6]2[CH:7]=[C:2]([C:47]3[CH:46]=[CH:45][C:44]([N:41]4[CH2:40][CH2:39][N:38]([C:36]([O:35][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:37])[CH2:43][CH2:42]4)=[CH:49][CH:48]=3)[CH:3]=[C:4]([O:12][C@@H:13]([C@@H:15]3[CH2:16][C:17](=[O:30])[N:18]([C@@H:20]([C:22]4[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=4)[CH3:21])[CH2:19]3)[CH3:14])[C:5]=12

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 52330144-(4-BOC-Piperazino)phenylboronic acidHCID 117842827HCID 117842827, compound

Product 1

HCID 117842929HCID 117842929, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

To an appropriate sized microwave vial, (R)-4-((R)-1-((6-bromo-3-chloropyrazolo[1,5-a]pyridin-4-yl)oxy)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one 6.36 (118 mg, 0.239 mmol), (4-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenyl)boronic acid (73.3 mg, 0.239 mmol), cesium carbonate (234 mg, 0.718 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 (27.7 mg, 0.0239 mmol) was added and the solution was heated at 100° C. for 18 h. After cooling to room temperature, the reaction was concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel to afford tert-butyl 4-(4-(3-chloro-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 6.38.

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

Sources & evidence

ORD record
ord-1e479e32c57d48c19290e12b4bd0b915
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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