Potassium Carbonate → HCID 67045860, compound

HRID 1923925Notes

Reaction equation

HRID 1923925 reaction equation
Br[C:2]1[C:3]([N:24]2[CH2:29][CH2:28][CH2:27][C@@H:26]([NH:30][C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:25]2)=[C:4]2[C:10]([NH:11][C:12]([CH:14]3[CH2:16][CH2:15]3)=[O:13])=[CH:9][N:8]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C:5]2=[N:6][CH:7]=1.[C:38](=O)([O-])[O-].[K+].[K+].CB1OB(C)OB(C)O1.CC#N.O>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:34]([O:33][C:31]([NH:30][C@@H:26]1[CH2:27][CH2:28][CH2:29][N:24]([C:3]2[C:2]([CH3:38])=[CH:7][N:6]=[C:5]3[N:8]([C:17]([O:19][C:20]([CH3:22])([CH3:21])[CH3:23])=[O:18])[CH:9]=[C:10]([NH:11][C:12]([CH:14]4[CH2:16][CH2:15]4)=[O:13])[C:4]=23)[CH2:25]1)=[O:32])([CH3:36])([CH3:37])[CH3:35]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 574072TrimethylboroxineHCID 18373917Acetonitrile--water (1/1)HCID 67045247HCID 67045247, compound

Product 1

HCID 67045860HCID 67045860, compoundYield 55.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

A solution of (R)-tert-butyl 5-bromo-4-(3-(tert-butoxycarbonylamino) piperidin-1-yl)-3-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (175 mg, 0.303 mmol) in dioxane (5 mL) at room temperature was treated with potassium carbonate (107 mg, 0.771 mmol), Pd(PPh3)4 (31.5 mg, 0.0272 mmol), and 2,4,6-trimethyl-1,3,5,2,4,6-trioxatriborinane (34.2 mg, 0.272 mmol). N2 was bubbled through the mixture for 5 minutes, and the mixture was heated at reflux for 24 hours under N2 atmosphere. The mixture was then diluted with EtOAc (20 mL) and washed with water (1×5 mL). The organic layer was separated, dried (MgSO4), filtered, and concentrated in vacuo. The residue obtained was purified by reverse phase chromatography (Biotage SP4, C-18 25M+, 40-95% CH3CN/water, 24 CV) to provide (R)-tert-butyl 4-(3-(tert-butoxycarbonylamino)piperidin-1-yl)-3-(cyclopropanecarboxamido)-5-methyl-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (86 mg, 55% yield) as a solid. LCMS (APCI+) m/z 514.1 (M+H)+.

Workup

  1. customN2 was bubbled through the mixture for 5 minutes
  2. temperaturethe mixture was heated
  3. temperatureat reflux for 24 hours under N2 atmosphere
  4. additionThe mixture was then diluted with EtOAc (20 mL)
  5. washwashed with water (1×5 mL)
  6. customThe organic layer was separated
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue obtained
  11. customwas purified by reverse phase chromatography (Biotage SP4

Sources & evidence

ORD record
ord-9276da3d7e8f4b328769ed0a5fee1a4e
Source dataset
uspto-grants-2012_05
Patent number
US08178131B2

Reaction notes

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