Potassium Phosphate, Tribasic → HCID 46865529, compound

HRID 216733Notes

Reaction equation

HRID 216733 reaction equation
Br[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([C:12]1[CH:17]=[CH:16][C:15]([N:18]3[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]3)=[CH:14][CH:13]=1)[CH:8]=[N:7]2.[F:25][C:26]1[CH:38]=[C:37](B2OC(C)(C)C(C)(C)O2)[CH:36]=[C:35]([F:48])[C:27]=1[CH2:28][N:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1.COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CC([O-])=O.CC([O-])=O.[Pd+2]>[F:48][C:35]1[CH:36]=[C:37]([C:2]2[CH:3]=[CH:4][CH:5]=[C:6]3[C:11]=2[N:10]=[C:9]([C:12]2[CH:17]=[CH:16][C:15]([N:18]4[CH2:19][CH2:20][N:21]([CH3:24])[CH2:22][CH2:23]4)=[CH:14][CH:13]=2)[CH:8]=[N:7]3)[CH:38]=[C:26]([F:25])[C:27]=1[CH2:28][N:29]1[CH2:30][CH2:31][O:32][CH2:33][CH2:34]1

Participants

6

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 59392637HCID 59392637, compoundHCID 593928518-Bromo-2-[4-(4-methyl-piperazin-1-yl)-phenyl]-quinoxaline

Product 1

HCID 46865529HCID 46865529, compound

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
105 °C

Procedure

A microwave tube is charged with 8-Bromo-2-[4-(4-methyl-piperazin-1-yl)-phenyl]-quinoxaline (2.6 g, 6.783 mmol), 4-[2,6-Difluoro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzyl]-morpholine (Step 87.1, 2.68 g, 7.12 mmol), S-Phos (258 mg, 0.611 mmol), K3PO4 (4.41 g, 20.4 mmol) and Pd(OAc)2 (45.68 mg, 0.203 mmol). After several cycles of vacuum/purge with argon, a mixture of 370 μl deionized water in 30 ml 1,2-dimethoxy-ethane is added. The reaction mixture is then heated to 105° C. for 12 h. After cooling, the reaction mixture is diluted with CH2Cl2, poured onto a saturated solution of NaHCO3 and extracted 3× with CH2Cl2. The combined organic layers are washed with water, brine, dried over Na2SO4, filtered and the filtrate is concentrated in vacuo. The residue is purified by chromatography (silicagel, CH2Cl2/CH2Cl2:EtOH:NH3 90:9:1 4:6) to afford the title compound as yellow solid, Rt=0.742 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: 516 (M+1)+.

Workup

  1. customAfter several cycles of vacuum/purge with argon
  2. additiona mixture of 370 μl
  3. additionis added
  4. temperatureAfter cooling
  5. additionthe reaction mixture is diluted with CH2Cl2
  6. additionpoured onto a saturated solution of NaHCO3
  7. extractionextracted 3× with CH2Cl2
  8. washThe combined organic layers are washed with water, brine
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationthe filtrate is concentrated in vacuo
  12. customThe residue is purified by chromatography (silicagel, CH2Cl2/CH2Cl2:EtOH:NH3 90:9:1 4:6)

Sources & evidence

ORD record
ord-f0aae2382e9f40c5b6d8a433aec385c7
Source dataset
uspto-grants-2012_06
Patent number
US08193189B2

Reaction notes

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