Potassium Phosphate, Tribasic → HCID 86684130, compound

HRID 1024032Notes

Reaction equation

HRID 1024032 reaction equation
Br[C:2]1[N:3]=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([N:18]3[CH2:23][CH2:22][N:21]([CH:24]4[CH2:27][O:26][CH2:25]4)[CH2:20][CH2:19]3)=[CH:14][N:13]=2)[C:5]2[N:6]([CH:8]=[CH:9][N:10]=2)[CH:7]=1.C(O[CH2:32][C:33]1[C:38](B2OC(C)(C)C(C)(C)O2)=[CH:37][C:36]([F:48])=[CH:35][C:34]=1[N:49]1[CH2:61][CH2:60][N:52]2[C:53]3[CH2:54][CH2:55][CH2:56][CH2:57][C:58]=3[CH:59]=[C:51]2[C:50]1=[O:62])(=O)C.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH3:71][C:72]([O-:74])=O.[Na+]>CC#N.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O1CCOCC1>[F:48][C:36]1[CH:37]=[C:38]([C:2]2[N:3]=[C:4]([NH:11][C:12]3[CH:17]=[CH:16][C:15]([N:18]4[CH2:23][CH2:22][N:21]([CH:24]5[CH2:25][O:26][CH2:27]5)[CH2:20][CH2:19]4)=[CH:14][N:13]=3)[C:5]3[N:6]([CH:8]=[CH:9][N:10]=3)[CH:7]=2)[C:33]([CH2:32][C:72](=[O:74])[CH3:71])=[C:34]([N:49]2[CH2:61][CH2:60][N:52]3[C:53]4[CH2:54][CH2:55][CH2:56][CH2:57][C:58]=4[CH:59]=[C:51]3[C:50]2=[O:62])[CH:35]=1

Participants

9

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 517045Sodium AcetateHCID 580442052-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-4-fluoro-6-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)benzyl AcetateHCID 86684131HCID 86684131, compound

Product 1

HCID 86684130HCID 86684130, compoundYield 72.5%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A 250-mL single-neck round-bottomed flask equipped with a magnetic stirrer and reflux condenser was charged with 1,4-dioxane (60 mL), 6-bromo-N-(5-(4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-yl)imidazo[1,2-a]pyrazin-8-amine (130 mg, 0.3 mmol), 4-fluoro-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acetate 101l (146 mg, 0.3 mmol), PdCl2(dppf) (25 mg, 0.03 mmol), K3PO4 (138 mg, 0.6 mmol), and NaOAc (48 mg, 0.6 mmol) in CH3CN (5 mL) and H2O (1.5 mL). The system was evacuated and refilled with N2. The reaction mixture was heated at 100° C. for 2 h. It was then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was purified by flash column chromatography eluting with 10:1 CH2Cl2/MeOH to afford 107a (150 mg, 70%) as a brown solid. MS: [M+H]+ 706.4.

Workup

  1. customA 250-mL single-neck round-bottomed flask equipped with a magnetic stirrer
  2. temperaturereflux condenser
  3. customThe system was evacuated
  4. additionrefilled with N2
  5. temperatureIt was then cooled to room temperature
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. customthe resulting residue was purified by flash column chromatography
  9. washeluting with 10:1 CH2Cl2/MeOH

Sources & evidence

ORD record
ord-758397c75f174acfac45a8e0b507d378
Source dataset
uspto-grants-2014_05
Patent number
US08722676B2

Reaction notes

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