Sodium Bicarbonate → HCID 58179870, compound

HRID 1518561Notes

Reaction equation

HRID 1518561 reaction equation
FC(F)(F)S(O[C:7]1[CH2:8][CH:9]2[N:14]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH:12]([CH:13]=1)[CH2:11][CH2:10]2)(=O)=O.C([O-])(O)=O.[Na+].[F:29][C:30]1[C:35]([F:36])=[CH:34][CH:33]=[CH:32][C:31]=1[N:37]1[C:41]([C:42]2[C:43]([NH2:57])=[N:44][CH:45]=[C:46](B3OC(C)(C)C(C)(C)O3)[CH:47]=2)=[N:40][N:39]=[N:38]1>COCCOC.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]>[NH2:57][C:43]1[N:44]=[CH:45][C:46]([C:7]2[CH2:8][CH:9]3[N:14]([C:15]([O:17][C:18]([CH3:19])([CH3:20])[CH3:21])=[O:16])[CH:12]([CH:13]=2)[CH2:11][CH2:10]3)=[CH:47][C:42]=1[C:41]1[N:37]([C:31]2[CH:32]=[CH:33][CH:34]=[C:35]([F:36])[C:30]=2[F:29])[N:38]=[N:39][N:40]=1

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 226480948-Boc-3-(trifluoromethylsulfonyloxy)-8-azabicyclo[3.2.1]oct-3-eneHCID 581794573-(1-(2,3-difluorophenyl)-1H-tetrazol-5-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine

Product 1

HCID 58179870HCID 58179870, compoundYield 51%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

A solution of tert-butyl 3-(trifluoromethylsulfonyloxy)-8-azabicyclo[3.2.1]oct-3-ene-8-carboxylate (50 mg, 140 μmol, 1.0 eq.) in DME (2 mL) was degassed with nitrogen for 15 minutes. NaHCO3 (1.2 mM solution, 350 μL, 420 μmol, 3 eq.) and 3-(1-(2,3-difluorophenyl)-1H-tetrazol-5-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine (56 mg, 140 μmol, 1.0 eq.) were added and degassing was continued for an additional 30 minutes. PdCl2(dppf)2 (10 mg, 14 μmol, 0.1 eq.) was added and degassing was continued for an additional 15 minutes. The reaction was sealed and microwaved at 90° C. for 15 minutes. After cooling, the organic layer was concentrated, NaHCO3 was added, and the product was extracted with EtOAc. Silica gel chromatography (EtOAc/hexanes) provided tert-butyl 3-(6-amino-5-(1-(2,3-difluorophenyl)-1H-tetrazol-5-yl)pyridin-3-yl)-8-azabicyclo[3.2.1]oct-3-ene-8-carboxylate (34 mg, 51% yield); 1H NMR (300 MHz, CDCl3): 8.25 (m, 1H); 7.6-7.25 (m, 3H); 7.07 (s, 1H); 6.4 (br s, 2H); 6.0 (m, 1H); 4.38 (m, 2H); 2.65 (m, 1H); 2.15 (m, 1H); 2.14-1.5 (m, 4H); 1.44 (s, 9H).

Workup

  1. customdegassing
  2. customdegassing
  3. waitwas continued for an additional 15 minutes
  4. customThe reaction was sealed
  5. custommicrowaved at 90° C. for 15 minutes
  6. temperatureAfter cooling
  7. concentrationthe organic layer was concentrated
  8. additionNaHCO3 was added
  9. extractionthe product was extracted with EtOAc

Sources & evidence

ORD record
ord-2a409b3277de4287b4ce5848027e9268
Source dataset
uspto-grants-2012_07
Patent number
US08232406B2

Reaction notes

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