Hydrochloric Acid → HCID 136414067, compound

HRID 1530567Notes

Reaction equation

HRID 1530567 reaction equation
Br[C:2]1[CH:24]=[CH:23][C:5]2[C:6]3[N:10]([CH2:11][CH2:12][O:13][C:4]=2[CH:3]=1)[CH:9]=[C:8]([C:14]1[N:15]([CH:20]([CH3:22])[CH3:21])[N:16]=[C:17]([CH3:19])[N:18]=1)[N:7]=3.[OH-:25].[K+].Cl>O1CCOCC1.O.CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>[CH:20]([N:15]1[C:14]([C:8]2[N:7]=[C:6]3[N:10]([CH2:11][CH2:12][O:13][C:4]4[CH:3]=[C:2]([OH:25])[CH:24]=[CH:23][C:5]=43)[CH:9]=2)=[N:18][C:17]([CH3:19])=[N:16]1)([CH3:22])[CH3:21]

Participants

9

Reactant 3

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 582043229-Bromo-2-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine

Product 1

HCID 136414067HCID 136414067, compoundYield 90%

Reagents, catalysts & solvents 5

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylCatalystHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 8-bromo-2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene (4.0 g, 10.3 mmol), KOH (1.73 g, 30.9 mmol), Pd2(dba)3 (189 mg, 0.2 mmol) and Xphos (350 mg, 0.82 mmol) in dioxane (20 mL) and H2O (10 mL) was purged with argon and heated at 90° C. for 45 min. The cooled reaction mixture was diluted with EtOAc and H2O then acidified with 1M HCl. The resulting precipitate was collected by filtration. The filtrate was separated, the aqueous phase extracted with further EtOAc and the combined organic extracts dried (MgSO4) and concentrated in vacuo. The resulting solid was combined with the original precipitate and triturated with Et2O. The resulting solid was collected by filtration and dried in vacuo affording 2-(2-Isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-8-ol as a white solid (3.01 g, 90%). LCMS: RT 2.36 min [M+H]+ 326.2

Workup

  1. customwas purged with argon
  2. customThe cooled reaction mixture
  3. filtrationThe resulting precipitate was collected by filtration
  4. customThe filtrate was separated
  5. extractionthe aqueous phase extracted with further EtOAc
  6. dry with materialthe combined organic extracts dried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customtriturated with Et2O
  9. filtrationThe resulting solid was collected by filtration
  10. customdried in vacuo

Sources & evidence

ORD record
ord-0144ca014b584667b7ece57d288f48d1
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

Loading…