Sodium Carbonate → 12-[1-(oxan-2-yl)-1H-pyrazol-5-yl]-4-[1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca-1(14),2,4,10,12-pentaene

HRID 1530557Notes

Reaction equation

HRID 1530557 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:13](=[CH:14][CH:15]=1)[C:12]1[N:8]([CH:9]=[C:10]([C:16]3[N:20]([CH:21]([CH3:23])[CH3:22])[N:19]=[CH:18][N:17]=3)[N:11]=1)[CH2:7][CH2:6][O:5]2.[O:24]1[CH2:29][CH2:28][CH2:27][CH2:26][CH:25]1[N:30]1[C:34](B(O)O)=[CH:33][CH:32]=[N:31]1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.CCO.O.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]>[O:24]1[CH2:29][CH2:28][CH2:27][CH2:26][CH:25]1[N:30]1[C:34]([C:2]2[CH:3]=[C:4]3[C:13](=[CH:14][CH:15]=2)[C:12]2[N:8]([CH:9]=[C:10]([C:16]4[N:20]([CH:21]([CH3:23])[CH3:22])[N:19]=[CH:18][N:17]=4)[N:11]=2)[CH2:7][CH2:6][O:5]3)=[CH:33][CH:32]=[N:31]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 467394631-(Tetrahydropyran-2-yl)pyrazole-5-boronic acidHCID 582043138-bromo-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene

Product 1

HCID 6831314112-[1-(oxan-2-yl)-1H-pyrazol-5-yl]-4-[1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca-1(14),2,4,10,12-pentaeneYield 92.5%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 86587095Dimethoxyethane ethanol waterSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 12-bromo-4-[1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca-1(14),2,4,10,12-pentaene (2.00 g, 5.34 mmol), 1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-ylboronic acid (1.58 g, 8.01 mmol), Pd(dppf)Cl2 (437 mg, 0.535 mmol), Na2CO3 (1.70 g, 16.0 mmol) in DME/EtOH/H2O (15/3/3 mL) was stirred at 100° C. for 1 hr under microwave irradiation. The mixture was extracted with EtOAc, washed with brine, dried over MgSO4, filtered, and evaporated to give crude product, which was purified by silica gel chromatography eluting with EtOAc/petroleum ether (1:5) to afford 12-[1-(oxan-2-yl)-1H-pyrazol-5-yl]-4-[1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca-1(14),2,4,10,12-pentaene (2.2 g, 90% yield) as white solid. LCMS (ESI) m/z: 446.3 [M+H+].

Workup

  1. extractionThe mixture was extracted with EtOAc
  2. washwashed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. customevaporated
  6. customto give crude product, which
  7. customwas purified by silica gel chromatography
  8. washeluting with EtOAc/petroleum ether (1:5)

Sources & evidence

ORD record
ord-c19389f56872478ab48344a234a42531
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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