8-bromo-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene → HCID 66558840, compound

HRID 1530573Notes

Reaction equation

HRID 1530573 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.Cl.[CH:25]([N:28]1[CH2:33][CH2:32][CH:31]([CH:34]2[CH2:38][CH2:37][CH2:36][NH:35]2)[CH2:30][CH2:29]1)([CH3:27])[CH3:26]>C1(C)C=CC=CC=1.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[CH:21]([N:20]1[C:16]([C:10]2[N:11]=[C:12]3[C:13]4[CH:14]=[CH:15][C:2]([N:35]5[CH2:36][CH2:37][CH2:38][CH:34]5[CH:31]5[CH2:30][CH2:29][N:28]([CH:25]([CH3:27])[CH3:26])[CH2:33][CH2:32]5)=[CH:3][C:4]=4[O:5][CH2:6][CH2:7][N:8]3[CH:9]=2)=[N:17][CH:18]=[N:19]1)([CH3:23])[CH3:22]

Participants

5

Reactant 2

HCID 582043138-bromo-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azuleneHCID 68312924HCID 68312924, compound

Product 1

HCID 66558840HCID 66558840, compoundYield 10.2%

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °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]tetradeca1(14),2,4,10,12-pentaene (300 mg, 0.800 mmol), 1-isopropyl-4-(pyrrolidin-2-yl)piperidine hydrochloride (163 mg, 0.800 mmol), Pd(PtBu3)2 (20 mg, 0.040 mmol), Na2OtBu (232 mg, 2.40 mol) in toluene (2 mL) in a seal tube was degassed with N2 for three times. The resulting mixture was stirred at 110° C. for 120 min. After the completion of the reaction, the solid was filtered off via Celite. The filtrate was concentrated and purified by prep-HPLC (Gilson GX 281, Shim-pack PRC-ODS 250 mm×20 mm×2, gradient: CH3CN/10 mm/L NH4HCO3, 17 min) to give racemic 175 (40 mg, 10% yield). The (R) and (S) enantiomers were separated by chiral-HPLC (OD-H column, 10% IPA in hexane isocratic) to give 7.0 mg one enantiomer and 10 mg the other enantiomer.

Workup

  1. customwas degassed with N2 for three times
  2. customAfter the completion of the reaction
  3. filtrationthe solid was filtered off via Celite
  4. concentrationThe filtrate was concentrated
  5. custompurified by prep-HPLC (Gilson GX 281, Shim-pack PRC-ODS 250 mm×20 mm×2, gradient: CH3CN/10 mm/L NH4HCO3, 17 min)

Sources & evidence

ORD record
ord-539b0c15622a4a439abdf90a63d6efd0
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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