Potassium Carbonate → HCID 57635356, compound

HRID 1971092Notes

Reaction equation

HRID 1971092 reaction equation
Br[C:2]1[N:6]2[CH2:7][CH2:8][N:9]([CH3:11])[CH2:10][C:5]2=[C:4]([C:12]([NH:14][C@@H:15]([CH2:20][CH:21]([CH3:23])[CH3:22])[C:16]([NH:18][CH3:19])=[O:17])=[O:13])[N:3]=1.C(=O)([O-])[O-].[K+].[K+].[C:30]1(B(O)O)[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>O1CCOCC1.O.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.[Pd]>[CH3:11][N:9]1[CH2:8][CH2:7][N:6]2[C:2]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)=[N:3][C:4]([C:12]([NH:14][C@@H:15]([CH2:20][CH:21]([CH3:23])[CH3:22])[C:16]([NH:18][CH3:19])=[O:17])=[O:13])=[C:5]2[CH2:10]1

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 57635645HCID 57635645, compound

Product 1

HCID 57635356HCID 57635356, compound

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of intermediate 20D (50 mg, 0.13 mmol), potassium carbonate (32 mg, 0.23 mmol), phenylboronic acid (0.20 mmol) and palladium tetrakis (8 mg) in dioxane (1.0 mL) and water (0.5 mL) was heated at 100° C. in a sealed vial overnight. After cooling down to room temperature, the mixture was passed through a thiol-based palladium scavenger. The residue was concentrated to dryness, to which MeOH (0.5 mL) was added. The solution was filtered to remove insoluble material and purified by preparative LC-MS using a gradient of 5% MeCN/water to 95 MeCN/water (0.1% formic acid) in 15 min. Pure fractions were evaporated with a Savant speedvac. The resulting oil was taken up in DCM (1.0 mL) and diluted with hexane (1.0 mL). Evaporation under air flow with mild heating gave Compound 275 as a white solid product (56% yield). LCMS (+ESI) m/z 384.1 [M+H]+.

Workup

  1. temperatureAfter cooling down to room temperature
  2. concentrationThe residue was concentrated to dryness, to which MeOH (0.5 mL)
  3. additionwas added
  4. filtrationThe solution was filtered
  5. customto remove insoluble material
  6. custompurified by preparative LC-MS
  7. customin 15 min
  8. customPure fractions were evaporated with a Savant speedvac
  9. additiondiluted with hexane (1.0 mL)
  10. customEvaporation under air flow
  11. temperaturewith mild heating

Sources & evidence

ORD record
ord-da13ea17bb744e2a91652bc018c00419
Source dataset
uspto-grants-2013_04
Patent number
US08431565B2

Reaction notes

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