Potassium Phosphate, Tribasic → HCID 67356926, compound

HRID 2405098Notes

Reaction equation

HRID 2405098 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]2[CH:8]=[CH:9][N:10]([CH:11]3[CH2:13][CH2:12]3)[C:4]=2[CH:3]=1.[CH2:14]=[C:15]([C:17]1[CH:25]=[CH:24][C:20]([C:21]([NH2:23])=[O:22])=[CH:19][CH:18]=1)[CH3:16].C(P(C(C)(C)C)C1C(C)=C(C)C(C)=C(C)C=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(O)(C)(C)C.O1CCOCC1>[CH:11]1([N:10]2[C:4]3[CH:3]=[C:2]([NH:23][C:21](=[O:22])[C:20]4[CH:24]=[CH:25][C:17]([C:15]([CH3:16])=[CH2:14])=[CH:18][CH:19]=4)[N:7]=[CH:6][C:5]=3[CH:8]=[CH:9]2)[CH2:13][CH2:12]1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 11953610Di-tert-butyl[3,4,5,6-tetramethyl-2',4',6'-tris(propan-2-yl)-[1,1'-biphenyl]-2-yl]phosphaneHCID 67327771HCID 67327771, compoundHCID 86762596HCID 86762596, compound

Product 1

HCID 67356926HCID 67356926, compoundYield 41.4%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6386tert-ButanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
130 °C

Procedure

In a 500 ml pressure vessel, 6-chloro-1-cyclopropyl-1H-pyrrolo[3,2-c]pyridine (7A, 6.2 g, 32 mmol), 4-(prop-1-en-2-yl)benzamide (6.2 g, 39 mmol), palladium(II)acetate (0.29 g, 1.3 mmol), and 2-di-tert-butylphosphino-3,4,5,6-tetramethyl-2′,4′,6′-triisopropyl-1,1′-biphenyl (2.2 g, 3.9 mmol) were added. Ground-up potassium phosphate tribasic (15 g, 45 mmol) was then added, followed by 1,4-dioxane (130 ml) and t-butanol (32 ml). The vessel was purged with nitrogen for 30 min, before being sealed and heated at 130° C. for 24 hr. After cooling, 250 ml of water and 250 ml EtOAc were successively added. The layers were separated, and the aqueous layer was extracted once more with 200 ml EtOAc. Combined organic layers were dried with Na2SO4, filtered, and concentrated. The crude product was purified by normal phase column chromatography eluting with EtOAc (10-40%) in hexanes. Product-containing fractions were combined and concentrated to obtain the product N-(1-cyclopropyl-1H-pyrrolo[3,2-c]pyridin-6-yl)-4-(prop-1-en-2-yl)benzamide (7B, ˜4.2 g, 41%) as a yellow solid.

Workup

  1. customThe vessel was purged with nitrogen for 30 min
  2. custombefore being sealed
  3. temperatureAfter cooling
  4. addition250 ml of water and 250 ml EtOAc were successively added
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted once more with 200 ml EtOAc
  7. dry with materialCombined organic layers were dried with Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product was purified by normal phase column chromatography
  11. washeluting with EtOAc (10-40%) in hexanes
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-2fd7588f400f44828eba44d91beec29b
Source dataset
uspto-grants-2014_08
Patent number
US08802695B2

Reaction notes

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