Sodium Carbonate → HCID 86661247, compound

HRID 1918945Notes

Reaction equation

HRID 1918945 reaction equation
[C:1]([O:4][CH2:5][C:6]1[C:11]([N:12]2[CH2:24][CH2:23][N:15]3[C:16]4[CH2:17][CH2:18][CH2:19][CH2:20][C:21]=4[CH:22]=[C:14]3[C:13]2=[O:25])=[CH:10][C:9]([F:26])=[CH:8][C:7]=1N1CCN2C3CCCCC=3C=C2C1=O)(=[O:3])[CH3:2].Br[C:42]1[CH:43]=[C:44]([NH:50][C:51]2[CH:55]=[C:54]([CH2:56][O:57][CH3:58])[N:53]([CH3:59])[N:52]=2)[C:45](=[O:49])[N:46]([CH3:48])[CH:47]=1.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.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]>[C:1]([O:4][CH2:5][C:6]1[C:11]([N:12]2[CH2:24][CH2:23][N:15]3[C:20]4[CH2:19][CH2:18][CH2:17][CH2:16][C:21]=4[CH:22]=[C:14]3[C:13]2=[O:25])=[CH:10][C:9]([F:26])=[CH:8][C:7]=1[C:42]1[CH:43]=[C:44]([NH:50][C:51]2[CH:55]=[C:54]([CH2:56][O:57][CH3:58])[N:53]([CH3:59])[N:52]=2)[C:45](=[O:49])[N:46]([CH3:48])[CH:47]=1)(=[O:3])[CH3:2]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 580441025-Bromo-3-(5-(methoxymethyl)-1-methyl-1H-pyrazol-3-ylamino)-1-methylpyridin-2(1H)-oneHCID 670164654-fluoro-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)-6-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)benzyl acetate

Product 1

HCID 86661247HCID 86661247, compoundYield 55.3%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

A sealed tube was charged with the mixture of 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 210d (230 mg, 0.48 mmol), 5-bromo-3-(5-(methoxymethyl)-1-methyl-1H-pyrazol-3-ylamino)-1-methylpyridin-2(1H)-one 176c (156 mg, 0.48 mmol), Pd(dppf)Cl2 (39 mg, 0.048 mmol), Na2CO3 (101 mg, 0.96 mmol) in DMF (18 mL). The system was evacuated and then refilled with N2. And the reaction mixture was heated at 110° C. for 2 h. Then, the mixture was cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was purified by column chromatography eluting with 15:1 methylene chloride/methanol to give 178a as a brown solid (160 mg, 53%). MS: [M+H]+ 603.

Workup

  1. customThe system was evacuated
  2. additionrefilled with N2
  3. temperatureThen, the mixture was cooled to room temperature
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe resulting residue was purified by column chromatography
  7. washeluting with 15:1 methylene chloride/methanol

Sources & evidence

ORD record
ord-62e21692be564e57be69397106069bdd
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

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