Potassium Phosphate, Tribasic → HCID 67045129, compound

HRID 1034822Notes

Reaction equation

HRID 1034822 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](=[O:16])[CH:13]([CH3:15])[CH3:14])=[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.[CH:38]1(B(O)O)[CH2:40][CH2:39]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].P(C1CCCCC1)(C1CCCCC1)C1CCCCC1>CC([O-])=O.CC([O-])=O.[Pd+2].CC#N.O.C1(C)C=CC=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]([CH:38]3[CH2:40][CH2:39]3)=[CH:7][N:6]=[C:5]3[N:8]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH:9]=[C:10]([NH:11][C:12](=[O:16])[CH:13]([CH3:15])[CH3:14])[C:4]=23)[CH2:25]1)=[O:32])([CH3:37])([CH3:35])[CH3:36]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 67045601HCID 67045601, compound

Product 1

HCID 67045129HCID 67045129, compoundYield 47.3%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Conditions

Temperature
80 °C

Procedure

(R)-tert-Butyl 5-bromo-4-(3-(tert-butoxycarbonylamino)piperidin-1-yl)-3-isobutyramido-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (0.340 g, 0.586 mmol), cyclopropylboronic acid (0.201 g, 2.34 mmol), K3PO4 (0.435 g, 2.05 mmol), Pd(OAc)2 (0.0131 g, 0.0586 mmol), and P(Cy)3 (0.0197 g, 0.0703 mmol) were placed in 10:1 toluene:water (4.4 mL total volume) and degassed under argon and then heated to 80° C. for 18 hours. The reaction was then cooled to room temperature, poured into water and extracted with DCM. The organic fraction was dried, filtered, and concentrated to give the crude product that was purified by reverse phase chromatography (Biotage SP4, C-18 25M+, 5-95% CH3CN/H2O) to give both (R)-tert-butyl 4-(3-(tert-butoxycarbonylamino)piperidin-1-yl)-5-cyclopropyl-3-isobutyramido-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (0.15 g, 47% yield) and a small amount of (R)-tert-butyl 4-(3-(tert-butoxycarbonylamino)piperidin-1-yl)-3-isobutyramido-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (0.01 g, 3% yield).

Workup

  1. customwater (4.4 mL total volume) and degassed under argon
  2. temperatureThe reaction was then cooled to room temperature
  3. additionpoured into water
  4. extractionextracted with DCM
  5. customThe organic fraction was dried
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give the crude product that
  9. customwas purified by reverse phase chromatography (Biotage SP4

Sources & evidence

ORD record
ord-98b2e797a34a49559e6b7458af670bf1
Source dataset
uspto-grants-2013_10
Patent number
US08545897B2

Reaction notes

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