Potassium Phosphate, Tribasic → HCID 59392739, compound

HRID 216735Notes

Reaction equation

HRID 216735 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9](Cl)[CH:8]=[N:7]2.[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][CH:23]([N:26]2[CH:30]=[C:29](B3OC(C)(C)C(C)(C)O3)[CH:28]=[N:27]2)[CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:13]([O:17][C:18]([N:20]1[CH2:21][CH2:22][CH:23]([N:26]2[CH:30]=[C:29]([C:9]3[CH:8]=[N:7][C:6]4[C:11](=[C:2]([Br:1])[CH:3]=[CH:4][CH:5]=4)[N:10]=3)[CH:28]=[N:27]2)[CH2:24][CH2:25]1)=[O:19])([CH3:16])([CH3:14])[CH3:15]

Participants

5

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 45480279tert-butyl 4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylateHCID 593926708-Bromo-2-chloroquinoxaline

Product 1

HCID 59392739HCID 59392739, compound

Reagents, catalysts & solvents 1

HCID 178418476HCID 178418476, compoundCatalyst

Conditions

Temperature
80 °C

Procedure

A microwave tube is charged with 8-Bromo-2-chloro-quinoxaline (Step 1.4, 1 g, 4.11 mmol), 4-[4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrazol-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (1.74 g, 3.70 mmol), K3PO4 (2.67 g, 12.3 mmol) and of PdCl2(PPh3)2 (88.2 mg, 0.123 mmol). After several cycles of vacuum/purge with argon, a mixture of 5 ml of DMA and 220 μl deionized water is added. The reaction mixture is then heated to 80° C. for 3 h. After cooling, the suspension is poured onto de-ionized water and diluted with EtOAc. The phases are separated and the aqueous phase re-extracted twice with EtOAc. The combined organic phases are washed with saturated brine and dried over Na2SO4. After filtration, the mixture is concentrated in vacuo. The residue is purified by chromatography on a 80 g silica gel column on a Combiflash Companion™ (Isco Inc.) apparatus (gradient hexanes:EtOAc from 1:0=>0:1) to afford the title compound as a yellow foam, Rt=1.350 min (Acquity HPLC BEH C18, 2.1×50 mm, 1.7 micron, detection 215 nM, 0.1 min 2% CH3CN in H2O, 2% to 100% CH3CN in H2O in 1.5 min, 0.4 min 100% CH3CN+0.1% TFA, flow rate 1.0 ml/min); MS: 458 (M+1, 79Br)+.

Workup

  1. customAfter several cycles of vacuum/purge with argon
  2. additiona mixture of 5 ml of DMA and 220 μl
  3. additionis added
  4. temperatureAfter cooling
  5. additionthe suspension is poured onto de-ionized water
  6. additiondiluted with EtOAc
  7. customThe phases are separated
  8. extractionthe aqueous phase re-extracted twice with EtOAc
  9. washThe combined organic phases are washed with saturated brine
  10. dry with materialdried over Na2SO4
  11. filtrationAfter filtration
  12. concentrationthe mixture is concentrated in vacuo
  13. customThe residue is purified by chromatography on a 80 g silica gel column on a Combiflash Companion™ (Isco Inc.) apparatus (gradient hexanes:EtOAc from 1:0=>0:1)

Sources & evidence

ORD record
ord-e7ca1b0138534eba978c30b397e40875
Source dataset
uspto-grants-2012_06
Patent number
US08193189B2

Reaction notes

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