Sodium Carbonate → HCID 67497592, compound

HRID 1628330Notes

Reaction equation

HRID 1628330 reaction equation
[N:1]1[CH:6]=[C:5](B(O)O)[CH:4]=[N:3][CH:2]=1.Br[C:11]1[CH:19]=[C:18]2[C:14]([CH2:15][CH2:16][N:17]2[C:20](=[O:37])[C@@H:21]([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])[CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[CH:13][CH:12]=1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C.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]>[O:37]=[C:20]([N:17]1[C:18]2[C:14](=[CH:13][CH:12]=[C:11]([C:5]3[CH:6]=[N:1][CH:2]=[N:3][CH:4]=3)[CH:19]=2)[CH2:15][CH2:16]1)[C@@H:21]([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:33])[CH3:34])[CH2:22][C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 67496344HCID 67496344, compound

Product 1

HCID 67497592HCID 67497592, compoundYield 74%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

Pyrimidin-5-ylboronic acid (28 mg, 230 μmol), (S)-tert-butyl 1-(6-bromoindolin-1-yl)-1-oxo-3-phenylpropan-2-ylcarbamate (100 mg, 230 μmol), (Pd(dppf)Cl2) (18 mg, 22 μmol) were dissolved in DMF (1.1 mL) and 1M sodium carbonate solution (630 μl, 630 μmol) was added. The resulting slurry was stirred in a sealed tube for one hour at 85° C., allowed to cool to room temperature and diluted with water. The mixture was extracted with ethyl acetate (2×50 mL). The organic layers were combined and washed with 1M lithium chloride solution (1×25 mL) and brine (1×25 mL) and dried over magnesium sulfate. The residue was purified by medium pressure chromatography (silica, 0 to 100% ethyl acetate:hexanes) to give (S)-tert-butyl 1-oxo-3-phenyl-1-(6-(pyrimidin-5-yl)indolin-1-yl)propan-2-ylcarbamate (74 mg, 74% yield). MS ESI (pos.) m/e: 445.1 (M+H).

Workup

  1. temperatureto cool to room temperature
  2. extractionThe mixture was extracted with ethyl acetate (2×50 mL)
  3. washwashed with 1M lithium chloride solution (1×25 mL) and brine (1×25 mL)
  4. dry with materialdried over magnesium sulfate
  5. customThe residue was purified by medium pressure chromatography (silica, 0 to 100% ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-7b75a10748d84d81a44d88224bb17e39
Source dataset
uspto-grants-2014_07
Patent number
US08785468B2

Reaction notes

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