Potassium Phosphate, Tribasic → HCID 67045129, compound

HRID 875823Notes

Reaction equation

HRID 875823 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-d8dacce1f81b4606a975192d4f4f3d73
Source dataset
uspto-grants-2015_03
Patent number
US08981085B2

Reaction notes

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