Sodium Carbonate → HCID 69620984, compound

HRID 1628329Notes

Reaction equation

HRID 1628329 reaction equation
[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[N:7]1[C:11](B2OC(C)(C)C(C)(C)O2)=[CH:10][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]>[O:48]=[C:31]([N:28]1[C:29]2[C:25](=[CH:24][CH:23]=[C:22]([C:11]3[N:7]([CH:2]4[CH2:3][CH2:4][CH2:5][CH2:6][O:1]4)[N:8]=[CH:9][CH:10]=3)[CH:30]=2)[CH2:26][CH2:27]1)[C@@H:32]([NH:40][C:41](=[O:47])[O:42][C:43]([CH3:46])([CH3:44])[CH3:45])[CH2:33][C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 115872081-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 67496344HCID 67496344, compound

Product 1

HCID 69620984HCID 69620984, compoundYield 29%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst2×HCID 962WaterSolvent

Conditions

Temperature
85 °C

Procedure

To DMF (1.1 ml) in a sealed tube flushed with nitrogen was added 1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (62 mg, 230 μmol), (S)-tert-butyl 1-(6-bromoindolin-1-yl)-1-oxo-3-phenylpropan-2-ylcarbamate (100 mg, 230 μmol), 1M sodium carbonate solution (630 μl, 630 μmol), 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. A significant amount of starting material remained. Another portion of (Pd(dppf)Cl2) (9.2 mg, 11 μmol) was added and the reaction was stirred for 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-oxo-3-phenyl-1-(6-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)indolin-1-yl)propan-2-ylcarbamate (34 mg, 29% yield). MS ESI (pos.) m/e: 433.1 (M+H-THP).

Workup

  1. customTo DMF (1.1 ml) in a sealed tube flushed with nitrogen
  2. stirringthe reaction was stirred for eight hours
  3. temperatureto cool to room temperature
  4. extractionextracted with ethyl acetate (2×40 mL)
  5. washThe combined organic layers were washed with 1M lithium chloride solution (1×30 mL) and brine (1×30 mL)
  6. dry with materialdried over magnesium sulfate
  7. customThe crude product was purified by medium pressure chromatography (silica, 0 to 60% ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-a4e82dd2ab1e431280b007b9a081fb38
Source dataset
uspto-grants-2014_07
Patent number
US08785468B2

Reaction notes

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