Trifluoroacetic acid → HCID 89995475, compound

HRID 1487330Notes

Reaction equation

HRID 1487330 reaction equation
[CH3:1][C:2]1([CH3:28])[C@H:7]([NH:8][C:9]2[C:10]3[N:11]([CH:18]=[C:19]([C:21]4[CH:22]=[N:23][N:24]([CH2:26][CH3:27])[CH:25]=4)[N:20]=3)[N:12]=[CH:13][C:14]=2[C:15]([NH2:17])=[O:16])[CH2:6][CH2:5][NH:4][CH2:3]1.C(O)(C(F)(F)F)=O.CCN(C(C)C)C(C)C.Cl[C:46]1[N:51]=[N:50][C:49]([C:52]#[N:53])=[CH:48][CH:47]=1>CN(C=O)C.CO>[C:52]([C:49]1[N:50]=[N:51][C:46]([N:4]2[CH2:5][CH2:6][C@@H:7]([NH:8][C:9]3[C:10]4[N:11]([CH:18]=[C:19]([C:21]5[CH:22]=[N:23][N:24]([CH2:26][CH3:27])[CH:25]=5)[N:20]=4)[N:12]=[CH:13][C:14]=3[C:15]([NH2:17])=[O:16])[C:2]([CH3:28])([CH3:1])[CH2:3]2)=[CH:47][CH:48]=1)#[N:53]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 133828716-Chloropyridazine-3-carbonitrileHCID 89995474HCID 89995474, compound

Product 1

HCID 89995475HCID 89995475, compoundYield 72.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of (R)-8-((3,3-dimethylpiperidin-4-yl)amino)-2-(1-ethyl-1H-pyrazol-4-yl)imidazo[1,2-b]pyridazine-7-carboxamide, TFA (13 mg, 0.026 mmol) in DMF (105 μl), DIEA (22.87 μl, 0.131 mmol) and 6-chloropyridazine-3-carbonitrile (4.02 mg, 0.029 mmol) were added. The reaction was heated at 90° C. After 2 hrs, the reaction was diluted with methanol (10 ml), filtered, and concentrated. The crude material was purified via preparative LC/MS (Method A). Fractions containing the desired product were combined and dried via centrifugal evaporation to afford the title compound of Example 53 (9.2 mg, 0.019 mmol, 72.4% yield). 1H NMR (500 MHz, methanol-d4) δ 8.33 (s, 1H), 7.95 (s, 1H), 7.93 (s, 1H), 7.89 (s, 1H), 7.60 (d, J=9.4 Hz, 1H), 7.22 (d, J=9.9 Hz, 1H), 5.77-5.67 (m, 1H), 4.33 (d, J=12.9 Hz, 1H), 4.26 (q, J=7.4 Hz, 2H), 3.49-3.41 (m, 1H), 3.26-3.19 (m, 1H), 2.35-2.27 (m, 1H), 1.91-1.80 (m, 1H), 1.54 (t, J=7.2 Hz, 3H), 1.43-1.38 (m, 1H), 1.14 (s, 3H), 1.10 (s, 3H). LC/MS (Method F): m/z 486.24 ([M+H]+), Rt. 1.400 min.

Workup

  1. filtrationfiltered
  2. concentrationconcentrated
  3. customThe crude material was purified via preparative LC/MS (Method A)
  4. additionFractions containing the desired product
  5. customdried via centrifugal evaporation

Sources & evidence

ORD record
ord-686c0a86d5f24122b1bb478fd29d33ca
Source dataset
uspto-grants-2016_08
Patent number
US09428511B2

Reaction notes

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