Sodium Bicarbonate → HCID 89827138, compound

HRID 2203240Notes

Reaction equation

HRID 2203240 reaction equation
[NH2:1][C:2]1[C:11]2[C:6](=[C:7](Br)[CH:8]=[CH:9][CH:10]=2)[N:5]=[N:4][C:3]=1[C:13]([NH2:15])=[O:14].[C:16]1([C:22]2[NH:26][C:25]3[CH:27]=[C:28](B4OC(C)(C)C(C)(C)O4)[CH:29]=[CH:30][C:24]=3[N:23]=2)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C([O-])(O)=O.[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O1CCOCC1>[NH2:1][C:2]1[C:11]2[C:6](=[C:7]([C:29]3[CH:28]=[CH:27][C:25]4[N:26]=[C:22]([C:16]5[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=5)[NH:23][C:24]=4[CH:30]=3)[CH:8]=[CH:9][CH:10]=2)[N:5]=[N:4][C:3]=1[C:13]([NH2:15])=[O:14]

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 68777686HCID 68777686, compoundHCID 69905525HCID 69905525, compound

Product 1

HCID 89827138HCID 89827138, compoundYield 32%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
140 °C

Procedure

4-Amino-8-bromocinnoline-3-carboxamide (0.040 g, 0.150 mmol), 2-phenyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzo[d]imidazole (0.048 g, 0.150 mmol), PdCl2(dppf) (5.48 mg, 7.50 μmol), dioxane (8 mL) and saturated NaHCO3 (2 mL) were combined and heated at 140° C. for 30 minutes in a microwave reactor. The reaction mixture was subsequently concentrated and purified via preparative HPLC (Phenomenex Gemini Prep 5 μm C18, 75×30 mm column) eluting with a gradient of 30-35% ACN/H2O (80/20 v/v, containing 10 mM NH4HCO3) in H2O (containing 10 mM NH4HCO3). The product-containing fractions were combined and acetonitrile was evaporated. The aqueous phase was diluted with saturated NaHCO3 and extracted with EtOAc. The organic phase was washed with water and the volatiles were evaporated to give the title compound as a light yellow solid (0.018 g, 32%). 1H NMR (400 MHz, DMSO-d6) δ ppm 7.47-7.65 (m, 4 H), 7.65-7.75 (m, 2 H), 7.83 (dd, J=8.21, 7.20 Hz, 1 H), 7.91-8.00 (m, 2 H), 8.23 (d, J=7.07 Hz, 2 H), 8.43 (d, J=7.58 Hz, 1 H), 8.54 (br s, 1 H); ESI-MS ma/z [(M+2H)/2]+ 191.1.

Workup

  1. concentrationThe reaction mixture was subsequently concentrated
  2. custompurified via preparative HPLC (Phenomenex Gemini Prep 5 μm C18, 75×30 mm column)
  3. washeluting with a gradient of 30-35% ACN/H2O (80/20 v/v, containing 10 mM NH4HCO3) in H2O (containing 10 mM NH4HCO3)
  4. customacetonitrile was evaporated
  5. additionThe aqueous phase was diluted with saturated NaHCO3
  6. extractionextracted with EtOAc
  7. washThe organic phase was washed with water
  8. customthe volatiles were evaporated

Sources & evidence

ORD record
ord-3921bbd24de24ae1b7b35972ffd3e4be
Source dataset
uspto-grants-2016_06
Patent number
US09365566B2

Reaction notes

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