Sodium Bicarbonate → HCID 89794893, compound

HRID 58121Notes

Reaction equation

HRID 58121 reaction equation
Br[C:2]1[C:3]([CH3:17])=[N:4][C:5]([N:8]2[CH2:13][C@@H:12]3[C@@H:10]([CH2:11]3)[CH:9]2[C:14]([OH:16])=[O:15])=[N:6][CH:7]=1.[F:18][C:19]([F:33])([F:32])[C:20]1[CH:28]=[C:27]2[C:23]([CH:24]=[N:25][NH:26]2)=[C:22](B(O)O)[CH:21]=1.C([O-])(O)=O.[Na+]>O1CCOCC1.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]>[CH3:17][C:3]1[C:2]([C:22]2[CH:21]=[C:20]([C:19]([F:33])([F:32])[F:18])[CH:28]=[C:27]3[C:23]=2[CH:24]=[N:25][NH:26]3)=[CH:7][N:6]=[C:5]([N:8]2[CH2:13][C@@H:12]3[C@@H:10]([CH2:11]3)[CH:9]2[C:14]([OH:16])=[O:15])[N:4]=1

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 89783507HCID 89783507, compound2×HCID 89794796(1R,5S)-3-(5-bromo-4-methylpyrimidin-2-yl)-3-azabicyclo[3.1.0]hexane-2-carboxylic acid

Product 1

HCID 89794893HCID 89794893, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
140 °C

Procedure

In a 10 mL microwave vial were mixed (1R,5S)-3-(5-bromo-4-methylpyrimidin-2-yl)-3-azabicyclo[3.1.0]hexane-2-carboxylic acid (200 mg, 0.671 mmol), (6-(trifluoromethyl)-1H-indazol-4-yl)boronic acid (201 mg, 0.872 mmol), PdCl2(dppf) (49.1 mg, 0.067 mmol), and aqueous NaHCO3 (1.435 mL, 2.68 mmol) in dioxane (10 mL) to give an orange suspension. The vial was sealed and heated in a microwave reactor to 140° C. for 40 minutes. Additional (6-(trifluoromethyl)-1H-indazol-4-yl)boronic acid (201 mg, 0.872 mmol) and PdCl2(dppf) (49.1 mg, 0.067 mmol) were added and heating was continued for 45 minutes. The reaction mixture was subsequently partitioned between water (50 mL) and EtOAc (50 mL). The phases were separated. The organic layer was discarded and the aqueous layer was acidified with 1N HCl and extracted with EtOAc (2×75 mL). The organic layers were combined, washed with brine (50 mL), dried over Na2SO4, filtered, and concentrated to give the title compound as a tan glass, which was used without further purification (170 mg, 62.8%).

Workup

  1. customto give an orange suspension
  2. customThe vial was sealed
  3. temperatureheating
  4. customThe reaction mixture was subsequently partitioned between water (50 mL) and EtOAc (50 mL)
  5. customThe phases were separated
  6. extractionextracted with EtOAc (2×75 mL)
  7. washwashed with brine (50 mL)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-30d76cb3e71d4693bf3681f45e5fe963
Source dataset
uspto-grants-2016_09
Patent number
US09434743B2

Reaction notes

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