Sodium Carbonate → HCID 67045884, compound

HRID 1923918Notes

Reaction equation

HRID 1923918 reaction equation
[CH3:1][C:2]1(C)[C:6](C)(C)OB(C(C)=C)O1.C(=O)([O-])[O-].[Na+].[Na+].Br[C:20]1[C:21]([N:42]2[CH2:47][CH2:46][CH2:45][C@@H:44]([NH:48][C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])[CH2:43]2)=[C:22]2[C:28]([NH:29][C:30]([CH:32]3[CH2:34][CH2:33]3)=[O:31])=[CH:27][N:26](C(OC(C)(C)C)=O)[C:23]2=[N:24][CH:25]=1>O1CCOCC1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH:32]1([C:30]([NH:29][C:28]2[C:22]3[C:23](=[N:24][CH:25]=[C:20]([C:2]([CH3:6])=[CH2:1])[C:21]=3[N:42]3[CH2:47][CH2:46][CH2:45][C@@H:44]([NH:48][C:49](=[O:50])[O:51][C:52]([CH3:53])([CH3:55])[CH3:54])[CH2:43]3)[NH:26][CH:27]=2)=[O:31])[CH2:34][CH2:33]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 109974264,4,5,5-Tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolaneHCID 67045247HCID 67045247, compound

Product 1

HCID 67045884HCID 67045884, compoundYield 62.1%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

4,4,5,5-Tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolane (436 mg, 2.59 mmol), PS-tetrakis (triphenylphosphine) palladium (786 mg, 0.0864 mmol, 0.10 mmol/1 g) and 2N sodium carbonate (1296 μL, 2.59 mmol) were added to (R)-tert-butyl 5-bromo-4-(3-(tert-butoxycarbonylamino)piperidin-1-yl)-3-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (500 mg, 0.864 mmol; Example 107, Step A) in degassed dioxane (1 mL). The reaction was heated to 120° C. for an hour under microwave irradiation. The reaction was then heated to 150° C. for 30 minutes. The reaction was filtered and extracted with DCM. The organic layer was concentrated, and the resulting residue was purified by reverse phase chromatography (Gilson, C-18, 5-95% CH3CN/water) to yield (R)-tert-butyl 1-(3-(cyclopropanecarboxamido)-5-(prop-1-en-2-yl)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (236 mg, 62% yield).

Workup

  1. temperatureThe reaction was then heated to 150° C. for 30 minutes
  2. filtrationThe reaction was filtered
  3. extractionextracted with DCM
  4. concentrationThe organic layer was concentrated
  5. customthe resulting residue was purified by reverse phase chromatography (Gilson, C-18, 5-95% CH3CN/water)

Sources & evidence

ORD record
ord-3fabeb1433724d42b494fb3fef7a46ad
Source dataset
uspto-grants-2012_05
Patent number
US08178131B2

Reaction notes

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