Potassium Phosphate, Tribasic → HCID 67045509, compound

HRID 408335Notes

Reaction equation

HRID 408335 reaction equation
Br[C:2]1[C:3]([N:25]2[CH2:30][CH2:29][CH2:28][C@@H:27]([NH:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:26]2)=[C:4]2[C:10]([NH:11][C:12](=[O:17])[CH2:13][CH2:14][O:15][CH3:16])=[CH:9][N:8]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[C:5]2=[N:6][CH:7]=1.[CH:39]1(B(O)O)[CH2:41][CH2:40]1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.O.CCOC(C)=O.O.C(O[Pd]OC(=O)C)(=O)C.CC#N.O>[C:35]([O:34][C:32]([NH:31][C@@H:27]1[CH2:28][CH2:29][CH2:30][N:25]([C:3]2[C:2]([CH:39]3[CH2:41][CH2:40]3)=[CH:7][N:6]=[C:5]3[N:8]([C:18]([O:20][C:21]([CH3:24])([CH3:22])[CH3:23])=[O:19])[CH:9]=[C:10]([NH:11][C:12](=[O:17])[CH2:13][CH2:14][O:15][CH3:16])[C:4]=23)[CH2:26]1)=[O:33])([CH3:38])([CH3:36])[CH3:37]

Participants

10

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 67045423HCID 67045423, compound

Product 1

HCID 67045509HCID 67045509, compoundYield 22.3%

Reagents, catalysts & solvents 5

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 18373917Acetonitrile--water (1/1)SolventHCID 22272177Toluene waterSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of (R)-tert-butyl 5-bromo-4-(3-(tert-butoxycarbonylamino)piperidin-1-yl)-3-(3-methoxypropanamido)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (370 mg, 0.620 mmol), cyclopropylboronic acid (213 mg, 2.48 mmol), tricyclohexylphosphine (20.9 mg, 0.0744 mmol), K3PO4 (461 mg, 2.17 mmol), and diacetoxypalladium (13.9 mg, 0.0620 mmol) in toluene/water (10:1 mixture, 9 mL) was stirred at 80° C. for 22 hours. The mixture was then diluted with EtOAc (60 mL) and water (10 mL) was added. The layers were separated, and the aqueous layer was extracted with EtOAc (3×20 mL). The combined organic layers were dried (MgSO4), filtered, and concentrated in vacuo. The oily residue was purified by reverse phase chromatography (Biotage SP4, C-18 25M+, 20%-90% CH3CN/water, 24CV) to provide (R)-tert-butyl 4-(3-(tert-butoxycarbonylamino)piperidin-1-yl)-5-cyclopropyl-3-(3-methoxypropanamido)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (77 mg, 22% yield) as a solid. LCMS (APCI+) m/z 558 (M+H)+.

Workup

  1. additionwas added
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted with EtOAc (3×20 mL)
  4. dry with materialThe combined organic layers were dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe oily residue was purified by reverse phase chromatography (Biotage SP4

Sources & evidence

ORD record
ord-070f5c2d74614975bbda2ee457f97074
Source dataset
uspto-grants-2014_06
Patent number
US08758830B2

Reaction notes

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