Sodium Carbonate → HCID 178508276, compound

HRID 1526661Notes

Reaction equation

HRID 1526661 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].Br[C:8]1[NH:12][C:11]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)=[N:10][N:9]=1.[F:20][CH:21]([F:46])[C@@:22]1([C:30]2[CH:35]=[C:34](B3OC(C)(C)C(C)(C)O3)[CH:33]=[CH:32][C:31]=2[F:45])[C@@H:28]2[C@@H:26]([CH2:27]2)[O:25][C:24]([NH2:29])=[N:23]1.O1CCOCC1>C(C1C(C(C)(C)C)=C([Pd]Cl)C=CC=1NC)(C)(C)C.O>[F:46][CH:21]([F:20])[C@@:22]1([C:30]2[CH:35]=[C:34]([C:8]3[NH:12][C:11]([C:13]4[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=4)=[N:10][N:9]=3)[CH:33]=[CH:32][C:31]=2[F:45])[C@@H:28]2[C@@H:26]([CH2:27]2)[O:25][C:24]([NH2:29])=[N:23]1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 90413479HCID 90413479, compoundHCID 178505576HCID 178505576, compound

Product 1

HCID 178508276HCID 178508276, compound

Reagents, catalysts & solvents 2

HCID 178482226HCID 178482226, compoundCatalystHCID 962WaterSolvent2×

Conditions

Temperature
120 °C

Procedure

A glass microwave reaction vessel was charged with sodium carbonate (0.171 g, 1.609 mmol), 3-bromo-5-(4-fluorophenyl)-4H-1,2,4-triazole (0.078 g, 0.322 mmol, US20130184248 A1), (1R,5S,6R)-5-(difluoromethyl)-5-(2-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-2-oxa-4-azabicyclo[4.1.0]hept-3-en-3-amine, 1,4-dioxane (2.5 ml) and water (0.83 ml). The vessel was capped and the solution was degassed by bubbling nitrogen gas through the solution for 10 minutes. Next, 1,1-bis[(di-t-butyl-p-methylaminophenyl]palladium(II) chloride (0.023 g, 0.032 mmol) was added and the vessel was sealed. The reaction mixture was stirred and heated in a Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Upssala, Sweden) at 120° C. for 20 minutes. The reaction was poured into water and the mixture was extracted with EtOAc. The combined organic extracts were washed with a 9:1 mixture of aqueous saturated ammonium chloride/ammonium hydroxide, saturated aqueous sodium chloride, and then stirred with activated carbon. The solution was filtered through a pad of celite and concentrated in vacuo to give the crude material. The crude material was purified by silica gel chromatography by eluting with 1:40 2M NH3.MeOH in CH2CL2, and then repurified by preparative TLC by eluting with 1:30 2M NH3.MeOH in CH2CL2 to provide the titled compound as a white solid after concentration with MeOH.

Workup

  1. customA glass microwave reaction vessel
  2. customThe vessel was capped
  3. customthe solution was degassed
  4. customby bubbling nitrogen gas through the solution for 10 minutes
  5. customthe vessel was sealed
  6. extractionthe mixture was extracted with EtOAc
  7. washThe combined organic extracts were washed with a 9:1 mixture of aqueous saturated ammonium chloride/ammonium hydroxide, saturated aqueous sodium chloride
  8. stirringstirred with activated carbon
  9. filtrationThe solution was filtered through a pad of celite
  10. concentrationconcentrated in vacuo
  11. customto give the crude material
  12. customThe crude material was purified by silica gel chromatography
  13. washby eluting with 1:40 2M NH3
  14. customMeOH in CH2CL2, and then repurified by preparative TLC
  15. washby eluting with 1:30 2M NH3

Sources & evidence

ORD record
ord-0eb5b231b1d640529875f38ddd8e248b
Source dataset
uspto-grants-2015_07
Patent number
US09085576B2

Reaction notes

Loading…