HCID 69894295, compound → HCID 69895900, compound

HRID 1794293Notes

Reaction equation

HRID 1794293 reaction equation
C(OC([N:8]1[CH2:13][CH:12]=[C:11]([C:14]2[CH:22]=[C:21]3[C:17]([CH2:18][N:19]4[C:25]([C:26]5[C:27]([C:32]6[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=6)=[N:28][O:29][C:30]=5[CH3:31])=[N:24][N:23]=[C:20]43)=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=O)(C)(C)C>C(O)(C(F)(F)F)=O>[CH3:31][C:30]1[O:29][N:28]=[C:27]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C:26]=1[C:25]1[N:19]2[CH2:18][C:17]3[C:21]([C:20]2=[N:23][N:24]=1)=[CH:22][C:14]([C:11]1[CH2:12][CH2:13][NH:8][CH2:9][CH:10]=1)=[CH:15][CH:16]=3

Participants

3

Reactant 1

HCID 69894295HCID 69894295, compound

Product 1

HCID 69895900HCID 69895900, compoundYield 77%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

4-[3-(5-Methyl-3-phenylisoxazol-4-yl)-5H-[1,2,4]triazolo[3,4-α]isoindol-8-yl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (750 mg, 1.52 mmol) was dissolved in TFA (10 ml) and stirred at room temperature for 30 minutes. The reaction was concentrated in vacuo and the residue was partitioned between ethyl acetate and saturated K2CO3 (aq). The organic layer was dried (MgSO4), filtered, concentrated in vacuo. The residue was purified by alumina chromatography, using dichloromethane→5% methanol/dichloromethane (in 1% methanol gradient) as the eluant, to yield the title compound (460 mg, 77%). 1H NMR (360 MHz, CDCl3) δ 8.02 (1H, d, J=1.04 Hz), 7.54–7.52 (2H, m), 7.47–7.38 (4H, m), 7.21 (1H, d, J=8.1 Hz), 6.23 (1H, t), 4.00 (2H, s), 3.59–3.58 (2H, m), 3.16 (2H, m), 2.71 (3H, s), 2.52–2.50 (2H, m). m/z (ES) 396 (M+H)+. d) 3-(5-Methyl-3-phenylisoxazol-4-yl)-8-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-5H-[1,2,4]triazolo[3,4-α]isoindole Under nitrogen atmosphere, 3-(5-Methyl-3-phenylisoxazol-4-yl)-8-(1,2,3,6-tetrahydropyridin-4-yl)-5H-[1,2,4]triazolo[3,4-α]isoindole (50 mg, 0.13 mmol) was dissolved in methanol (2 ml) and formalin solution (65 μl, 0.8 mmol) and sodium cyanoborohydride (32 mg, 0.52 mmol) were added. The reaction was stirred at room temperature for 3 hours. The reaction was concentrated in vacuo and partitioned between ethyl acetate and water. The organic layer was washed with saturated NaCl (aq), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by alumina chromatography eluting with dichloromethane→2% methanol/dichloromethane (in 0.5% methanol gradient) to yield the title compound (21 mg, 41%). 1H NMR (400 MHz, d4 McOH) δ 8.01 (1H, d, J=1.3 Hz), 7.59 (1H, dd, J=1.6, 8.2 Hz), 7.52–7.42 (5H, m), 7.40 (1H, d, J=8.2 Hz), 6.28–6.27 (1H m), 4.31 (2H, s), 3.21–3.20 (2H, m), 2.78 (2H, m), 2.69–2.66 (2H, m), 2.64 (3H, s), 2.43 (3H, s).

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. customthe residue was partitioned between ethyl acetate and saturated K2CO3 (aq)
  3. dry with materialThe organic layer was dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by alumina chromatography

Sources & evidence

ORD record
ord-a3e265136b8a4206aa527c582e8d9704
Source dataset
uspto-grants-2006_04
Patent number
US07022724B2

Reaction notes

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