1-(7-Amino-3,4-dihydroisoquinolin-2(1H)-YL)-2,2,2-trifluoroethanone → Trifluoroacetamide pyrazolopyridazine

HRID 1159897Notes

Reaction equation

HRID 1159897 reaction equation
ClC1N=C(C2C(C3C=C(NC(=O)C4C(F)=CC=CC=4F)C=CC=3)=[N:10][N:11]3C=CC=CC=23)C=CN=1.[F:34][C:35]([F:50])([F:49])[C:36]([N:38]1CCC2[C:40](=[CH:41][C:42]([NH2:48])=[CH:43]C=2)[CH2:39]1)=[O:37]>CC(O)C>[NH:10]1[C:41]2[CH:40]=[CH:39][N:38]=[N:48][C:42]=2[CH:43]=[N:11]1.[F:34][C:35]([F:50])([F:49])[C:36]([NH2:38])=[O:37]

Participants

4

Reactant 2

HCID 107527801-(7-Amino-3,4-dihydroisoquinolin-2(1H)-YL)-2,2,2-trifluoroethanoneHCID 59513803N-{3-[3-(2-Chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2,6-difluorobenzamide

Product 1

HCID 86618777Trifluoroacetamide pyrazolopyridazineYield 349.1%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
160 °C

Procedure

A mixture of N-{3-[3-(2-chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2,6-difluorobenzamide (200 mg, 0.43 mmol) and 2-(trifluoroacetyl)-1,2,3,4-tetrahydro-7-isoquinolinamine (211 mg, 0.86 mmol) in a few mL i-PrOH was heated in a microwave apparatus at 160° C. until the reaction was complete. The by partitioning the reaction mixture between saturated aqueous NaHCO3 and CHCl3. The organic layer was washed with brine, dried over Na2SO4, filtered and concentrated to give a residue that was purified by silica gel chromatography to afford the intermediate trifluoroacetamide pyrazolopyridazine (350 mg). A portion of this material (250 mg) was subjected to similar conditions as described in Example 62, step F to afford the title compound (198 mg) as a tan powder. LC-MS (AP)+=574.07. 1H NMR (400 MHz, DMSO-d6) δ 2.59 (t, 2H, J=5.5), 2.89 (t, 2H, J=5.5), 3.74 (s, 2H), 6.46 (d, 1H, J=5.1), 6.90 (d, 1H, J=8.2), 7.10 (t, 1H, J=6.7), 7.22 (d, 1H, J=8.0), 7.24 (d, 1H, J=7.9), 7.32 (s, 1H, 7.34 (s, 1H), 7.44-7.48 (m, 3H), 7.53-7.60 (m, 1H), 7.80 (d, 1H, J=8.0), 7.97 (s, 1H), 8.21 (d, 1H, J=5.3), 8.46 (d, 1H, J=9.1), 8.82 (d, 1H, J=6.7), 9.37 (s, 1H).

Workup

  1. customThe by partitioning the reaction mixture between saturated aqueous NaHCO3 and CHCl3
  2. washThe organic layer was washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give a residue that
  7. customwas purified by silica gel chromatography

Sources & evidence

ORD record
ord-623f42e7bad04e7b8c8a46cd85a44a54
Source dataset
uspto-grants-2010_10
Patent number
US07812022B2

Reaction notes

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