Potassium Phosphate, Tribasic → (E)-7-(morpholine-4-carbonyl)-3-styryl-9H-carbazole-1-carboxamide

HRID 2410931Notes

Reaction equation

HRID 2410931 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:23]([NH2:25])=[O:24])[C:5]2[NH:6][C:7]3[C:12]([C:13]=2[CH:14]=1)=[CH:11][CH:10]=[C:9]([C:15]([N:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1)=[O:16])[CH:8]=3.[CH:26](/B(O)O)=[CH:27]\[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[N:17]1([C:15]([C:9]2[CH:8]=[C:7]3[C:12]([C:13]4[CH:14]=[C:2](/[CH:26]=[CH:27]/[C:28]5[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=5)[CH:3]=[C:4]([C:23]([NH2:25])=[O:24])[C:5]=4[NH:6]3)=[CH:11][CH:10]=2)=[O:16])[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 5702628Styrylboronic acidHCID 666047593-bromo-7-(morpholine-4-carbonyl)-9H-carbazole-1-carboxamide

Product 1

HCID 66605057(E)-7-(morpholine-4-carbonyl)-3-styryl-9H-carbazole-1-carboxamideYield 3.3%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
130 °C

Procedure

3-Bromo-7-(morpholine-4-carbonyl)-9H-carbazole-1-carboxamide (40 mg, 0.10 mmol, Example 144A) and dicyclohexy(2′,6′-dimethoxybiphenyl-2)phosphine (8.2 mg) were dissolved in dioxane (1.5 mL) and added into a 2-ml microwave vial containing (E)-styrylboronic acid (37 mg, 0.25 mmol), followed by addition of potassium phosphate (64 mg in 0.15 mL water) into above vials. Pd(OAc)2 (4.49 mg, 20.00 μmol) was added as solid. The vial was sealed and heated to 130° C. for 10 minutes. The crude reaction mixture was evaporated to dryness, dissolved in DMF+MeOH (1.2 mL+0.4 mL), filtered and purified by preparative HPLC. Product containing fractions were combined and evaporated to dryness to give 1.4 mg (E)-7-(morpholine-4-carbonyl)-3-styryl-9H-carbazole-1-carboxamide. HPLC retention time 4.39 min. (SUPELCO® Ascentis Express 4.5×50 mm 3 um C18, 2 ml/min, 5 to 95% B in 8 minutes, then 95% B for 1 minute. Solvent A: 5% CH3CN—95% H2O—10 mM NH4OAc; Solvent B: 95% CH3CN—5% H2O—10 mM NH4OAc). MS (ESI) m/e+=426 [M+H]+.

Workup

  1. additionadded into a 2-ml microwave vial
  2. customThe vial was sealed
  3. customThe crude reaction mixture
  4. customwas evaporated to dryness
  5. dissolutiondissolved in DMF+MeOH (1.2 mL+0.4 mL)
  6. filtrationfiltered
  7. custompurified by preparative HPLC
  8. additionProduct containing fractions
  9. customevaporated to dryness

Sources & evidence

ORD record
ord-7e8d2017a4044d038d18199868a43aeb
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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