Potassium Phosphate, Tribasic → HCID 86683766, compound

HRID 1026499Notes

Reaction equation

HRID 1026499 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([N:17]3[CH2:22][CH2:21][N:20]([CH:23]4[CH2:26][O:25][CH2:24]4)[CH2:19][C:18]3([CH3:28])[CH3:27])=[CH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[C:29]([O:32][CH2:33][C:34]1[C:39](B2OC(C)(C)C(C)(C)O2)=[CH:38][C:37]([F:49])=[CH:36][C:35]=1[N:50]1[CH2:62][CH2:61][N:53]2[C:54]3[CH2:55][CH2:56][CH2:57][CH2:58][C:59]=3[CH:60]=[C:52]2[C:51]1=[O:63])(=[O:31])[CH3:30].[O-]P([O-])([O-])=O.[K+].[K+].[K+].C([O-])(=O)C.[Na+]>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].O.C(#N)C>[C:29]([O:32][CH2:33][C:34]1[C:35]([N:50]2[CH2:62][CH2:61][N:53]3[C:54]4[CH2:55][CH2:56][CH2:57][CH2:58][C:59]=4[CH:60]=[C:52]3[C:51]2=[O:63])=[CH:36][C:37]([F:49])=[CH:38][C:39]=1[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([N:17]3[CH2:22][CH2:21][N:20]([CH:23]4[CH2:24][O:25][CH2:26]4)[CH2:19][C:18]3([CH3:27])[CH3:28])=[CH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1)(=[O:31])[CH3:30]

Participants

8

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 86683765HCID 86683765, compound

Product 1

HCID 86683766HCID 86683766, compoundYield 29.6%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
90 °C

Procedure

A 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 125e (190 mg, 1.0 eq., 0.42 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-tetra-methyl-1,3,2-dioxaborolan-2-yl)benzyl acetate 115m (405 mg, 2.0 eq., 0.84 mmol), PdCl2(dppf) (33 mg, 0.10 eq., 0.040 mmol), K3PO4 (178 mg, 2.0 eq., 0.84 mmol), sodium acetate (69 mg, 2.0 eq., 0.84 mmol), acetonitrile (20 mL), and water (0.1 mL). After three cycles of vacuum/argon flush, the mixture was heated at 90° 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 silica-gel column chromatography eluting with 50:1 dichloromethane/ethanol to afford 125f (90 mg, 29%) as yellow solid. MS: [M+H]+ 724.3.

Workup

  1. customA 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customAfter three cycles of vacuum/argon flush
  3. temperatureIt was then cooled to room temperature
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe resulting residue was purified by silica-gel column chromatography
  7. washeluting with 50:1 dichloromethane/ethanol

Sources & evidence

ORD record
ord-4ac0f5ff82444b77831c75cc8a90987a
Source dataset
uspto-grants-2014_05
Patent number
US08729072B2

Reaction notes

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