Dimethylformamide → HCID 69620982, compound

HRID 1628327Notes

Reaction equation

HRID 1628327 reaction equation
CN(C=O)C.[CH3:6][N:7]1[CH:11]=[C:10](B2OC(C)(C)C(C)(C)O2)[CH:9]=[N:8]1.Br[C:22]1[CH:30]=[C:29]2[C:25]([CH2:26][CH2:27][N:28]2[C:31](=[O:48])[C@@H:32]([NH:40][C:41](=[O:47])[O:42][C:43]([CH3:46])([CH3:45])[CH3:44])[CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)=[CH:24][CH:23]=1.C(=O)([O-])[O-].[Na+].[Na+]>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]>[CH3:6][N:7]1[CH:11]=[C:10]([C:22]2[CH:30]=[C:29]3[C:25]([CH2:26][CH2:27][N:28]3[C:31](=[O:48])[C@@H:32]([NH:40][C:41](=[O:47])[O:42][C:43]([CH3:44])([CH3:46])[CH3:45])[CH2:33][C:34]3[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=3)=[CH:24][CH:23]=2)[CH:9]=[N:8]1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 67496344HCID 67496344, compound

Product 1

HCID 69620982HCID 69620982, compoundYield 67%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
85 °C

Procedure

To DMF (11 ml, 225 μmol) in a sealed tube flushed with nitrogen was added 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (47 mg, 0.225 mmol), (S)-tert-butyl 1-(6-bromoindolin-1-yl)-1-oxo-3-phenylpropan-2-ylcarbamate (100 mg, 225 μmol), sodium carbonate solution (629 μl, 629 mmol), and 1,1′-dis(diphenylphosphino)ferrocene-palladium (II) dichloride dichloromethane complex (Pd(dppf)Cl2) (9.2 mg, 11 μmol). The slurry was heated to 85° C. and stirred for three hours. LCMS indicated a trace of starting material remained. Another aliquot of Pd(dppf)Cl2 (9.2 mg, 11 μmol) was added and the slurry stirred for an additional eight hours. The reaction was then allowed to cool to room temperature. The reaction was diluted with water and extracted with ethyl acetate (2×40 mL). The combined organic layers were washed with 1M lithium chloride solution (1×30 mL) and brine (1×30 mL) and dried over magnesium sulfate. The crude product was purified by medium pressure chromatography (silica, 0 to 60% ethyl acetate:hexanes) to give tert-butyl (S)-1-(6-(1-methyl-1H-pyrazol-4-yl)indolin-1-yl)-1-oxo-3-phenylpropan-2-ylcarbamate (67 mg, 67%). MS ESI (pos.) m/e: 447.3 (M+H).

Workup

  1. stirringthe slurry stirred for an additional eight hours
  2. temperatureto cool to room temperature
  3. extractionextracted with ethyl acetate (2×40 mL)
  4. washThe combined organic layers were washed with 1M lithium chloride solution (1×30 mL) and brine (1×30 mL)
  5. dry with materialdried over magnesium sulfate
  6. customThe crude product was purified by medium pressure chromatography (silica, 0 to 60% ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-9aee9b98fbf34e9799c689a898404e28
Source dataset
uspto-grants-2014_07
Patent number
US08785468B2

Reaction notes

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