Hydrochloric Acid → HCID 58204851, compound

HRID 886285Notes

Reaction equation

HRID 886285 reaction equation
Br[C:2]1[CH:22]=[CH:21][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]([CH3:20])[N:16]=[C:17]([CH3:19])[N:18]=1)[N:7]=3.C([O-])(=O)C.[K+].O1CCCCC1[O:34][CH2:35][CH2:36][N:37]1[CH:41]=[C:40](B2OC(C)(C)C(C)(C)O2)[CH:39]=[N:38]1.Cl>C(#N)C.O.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>[CH3:20][N:15]1[C:14]([C:8]2[N:7]=[C:6]3[C:5]4[CH:21]=[CH:22][C:2]([C:40]5[CH:39]=[N:38][N:37]([CH2:36][CH2:35][OH:34])[CH:41]=5)=[CH:3][C:4]=4[O:13][CH2:12][CH2:11][N:10]3[CH:9]=2)=[N:18][C:17]([CH3:19])=[N:16]1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 517044Potassium AcetateHCID 58204297HCID 58204297, compoundHCID 593418191-[2-(oxan-2-yloxy)ethyl]-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

Product 1

HCID 58204851HCID 58204851, compoundYield 14.7%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
140 °C

Procedure

To a microwave vial was added 8-Bromo-2-(2,5-dimethyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene (0.150 g, 0.000416 mol) and Potassium acetate (0.123 g, 0.00125 mol) in Acetonitrile (2.0 mL) and Water (2.0 mL). The solution was thoroughly purged with N2. 1-[2-(Tetrahydro-pyran-2-yloxy)-ethyl]-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (0.148 g, 0.000458 mol) and Tetrakis(triphenylphosphine)palladium(0) (0.0481 g, 0.0000416 mol) were added and the vial was immediately sealed. The reaction was heated in the microwave to 140° C. for 20 minutes. The mixture was partitioned between saturated NH4Cl and methylene chloride and extracted 3 times with methylene chloride. The organic phases were combined, dried with MgSO4, and concentrated. The crude was dissolved in methylene chloride (5.0 mL) and hydrogen chloride (0.00125 mol, 4N in dioxane, 0.31 mL) was added dropwise. The reaction was stirred at room temperature for 1 hour. The mixture was concentrated and partitioned between saturated sodium bicarbonate and methylene chloride and extracted 3 times with methylene chloride. Most of the product precipitated in the aqueous phase—the mixture was filtered and submitted to reverse-phase HPLC, then recrystallized in EtOH/MeOH to afford 24 mg 285 as a white solid. MS (ESI+) 392.2. 1H NMR (500 MHz, DMSO) δ 8.40 (d, J=8.4 Hz, 1H), 8.22 (s, 1H), 7.94 (s, 1H), 7.88 (s, 1H), 7.36 (dd, J=8.4, 1.7 Hz, 1H), 7.27 (d, J=1.7 Hz, 1H), 4.90 (t, J=5.3 Hz, 1H), 4.54-4.48 (m, 4H), 4.21 (s, 3H), 4.16 (t, J=5.7 Hz, 2H), 3.77 (q, J=5.6 Hz, 2H), 2.24 (s, 3H)

Workup

  1. customThe solution was thoroughly purged with N2
  2. customthe vial was immediately sealed
  3. customThe mixture was partitioned between saturated NH4Cl and methylene chloride
  4. extractionextracted 3 times with methylene chloride
  5. dry with materialdried with MgSO4
  6. concentrationconcentrated
  7. dissolutionThe crude was dissolved in methylene chloride (5.0 mL)
  8. concentrationThe mixture was concentrated
  9. custompartitioned between saturated sodium bicarbonate and methylene chloride
  10. extractionextracted 3 times with methylene chloride
  11. customMost of the product precipitated in the aqueous phase—the mixture
  12. filtrationwas filtered
  13. customrecrystallized in EtOH/MeOH

Sources & evidence

ORD record
ord-961790c0d3e64aacbfa2c0e9cb0b24b9
Source dataset
uspto-grants-2012_08
Patent number
US08242104B2

Reaction notes

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