Lithium Chloride → 12-(1-ethoxyethenyl)-13-methyl-4-[1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca1(14),2,4,10,12-pentaene

HRID 1530663Notes

Reaction equation

HRID 1530663 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:13](=[CH:14][C:15]=1[CH3:16])[C:12]1[N:8]([CH:9]=[C:10]([C:17]3[N:21]([CH:22]([CH3:24])[CH3:23])[N:20]=[CH:19][N:18]=3)[N:11]=1)[CH2:7][CH2:6][O:5]2.C([Sn](CCCC)(CCCC)[C:30]([O:32][CH2:33][CH3:34])=[CH2:31])CCC.[Li+].[Cl-].[F-].[K+]>C1COCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:33]([O:32][C:30]([C:2]1[CH:3]=[C:4]2[C:13](=[CH:14][C:15]=1[CH3:16])[C:12]1[N:8]([CH:9]=[C:10]([C:17]3[N:21]([CH:22]([CH3:24])[CH3:23])[N:20]=[CH:19][N:18]=3)[N:11]=1)[CH2:7][CH2:6][O:5]2)=[CH2:31])[CH3:34]

Participants

7

Reactant 4

HCID 433294Lithium ChlorideHCID 522689Potassium FluorideHCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 6831318012-bromo-13-methyl-4-[1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca1(14),2,4,10,12-pentaene

Product 1

HCID 6831291912-(1-ethoxyethenyl)-13-methyl-4-[1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca1(14),2,4,10,12-pentaeneYield 68%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 12-bromo-13-methyl-4-[1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca1(14),2,4,10,12-pentaene (1.0 g, 2.6 mmol), tributyl(1-ethoxyvinyl)stannane (1.2 mL), Pd(PPh3)4 (90 mg, 7.8 mmol), and LiCl (328 mg, 7.8 mmol) in dry THF (10 mL) was stirred at 70° C. for 48 h under nitrogen atmosphere. KF (100 mL, 0.16 M) was added and the mixture was further stirred at room temperature for 1 h. The solid was filtered off. The filtrate was concentrated to give the crude product, which was purified by reverse phase Combiflash eluting with a 0-50% gradient of CH3CN in 0.3% NH4HCO3 to afford 12-(1-ethoxyethenyl)-13-methyl-4-[1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca1(14),2,4,10,12-pentaene (660 mg, 68% yield). LCMS (ESI) m/z: 380.2 [M+H+].

Workup

  1. stirringthe mixture was further stirred at room temperature for 1 h
  2. filtrationThe solid was filtered off
  3. concentrationThe filtrate was concentrated
  4. customto give the crude product, which
  5. customwas purified by reverse phase Combiflash
  6. washeluting with a 0-50% gradient of CH3CN in 0.3% NH4HCO3

Sources & evidence

ORD record
ord-fd54d4dc50c148b6bf2baf6d8db252f8
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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