Hydrochloric Acid → 3-(4-Fluoro-phenyl)-2-isopropyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene

HRID 606625Notes

Reaction equation

HRID 606625 reaction equation
C(OC(=O)[NH:10][CH2:11][CH2:12][C:13]1[C:17]([CH2:18][CH:19]2OCCO2)=[C:16]([C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=2)[N:15]([CH:31]([CH3:33])[CH3:32])[N:14]=1)C1C=CC=CC=1.Cl.N#N>[Pd].C(O)(CC)(C)C>[F:30][C:27]1[CH:28]=[CH:29][C:24]([C:16]2[N:15]([CH:31]([CH3:33])[CH3:32])[N:14]=[C:13]3[C:17]=2[CH2:18][CH2:19][NH:10][CH2:11][CH2:12]3)=[CH:25][CH:26]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 947NitrogenHCID 54754013{2-[4-[1,3]Dioxolan-2-ylmethyl-5-(4-fluoro-phenyl)-1-isopropyl-1H-pyrazol-3-yl]-ethyl}-carbamic acid benzyl ester

Product 1

HCID 113916543-(4-Fluoro-phenyl)-2-isopropyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 64052-Methyl-2-butanolSolvent

Conditions

Temperature
0 °C

Procedure

To a 2.2 L Parr hydrogenation flask was added {2-[4-[1,3]dioxolan-2-ylmethyl-5-(4-fluoro-phenyl)-1-isopropyl-1H-pyrazol-3-yl]-ethyl}-carbamic acid benzyl ester (90.0 g, 0.193 mol), t-amyl alcohol (910 mL), and 3 N HCl (190 mL, 0.570 mol). The flask was charged with N2(g) and 10% Pd/C (22.2 g) was added. The reaction mixture was hydrogenated at 40 psi and at 45° C. for 18 h. The mixture was filtered through acid-treated, low metal filter paper. The filtrate was concentrated to oil, diluted with water (500 mL), and washed with EtOAc (3×250 mL). The aqueous mixture was cooled to 0° C. and basified to pH 13-14 by the addition of KOH pellets. The aqueous solution was extracted with EtOAc (3×250 mL). The combined organic layers were filtered through acid-treated filter paper. The filtrate was dried (Na2SO4) and concentrated to give the title compound. MS (ESI): exact mass calcd. for C16H20FN3, 273.16; m/z found, 274.3 [M+H]+. 1H NMR (400 MHz, CDCl3): 7.25-7.20 (m, 2H), 7.18-7.13 (t, J=8.6, 2H), 4.28-4.21 (sept, J=6.6, 1H), 3.04-3.01 (m, 2H), 2.94-2.88 (m, 4H), 2.46 (t, J=5.2, 2H), 1.40 (d, J=6.6, 6H).

Workup

  1. additionwas added
  2. filtrationThe mixture was filtered
  3. additionthrough acid-treated
  4. filtrationlow metal filter paper
  5. concentrationThe filtrate was concentrated to oil
  6. additiondiluted with water (500 mL)
  7. washwashed with EtOAc (3×250 mL)
  8. extractionThe aqueous solution was extracted with EtOAc (3×250 mL)
  9. filtrationThe combined organic layers were filtered
  10. additionthrough acid-treated
  11. filtrationfilter paper
  12. dry with materialThe filtrate was dried (Na2SO4)
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-80ae42c957424cfea823f4d5c4fc96f3
Source dataset
uspto-grants-2011_03
Patent number
US07915404B2

Reaction notes

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