Trifluoroacetic acid → HCID 89995491, compound

HRID 1487321Notes

Reaction equation

HRID 1487321 reaction equation
[CH2:1]([N:3]1[CH:7]=[C:6]([C:8]2[N:9]=[C:10]3[C:15]([NH:16][C@H:17]4[C@@H:21]([CH3:22])[CH2:20][NH:19][CH2:18]4)=[C:14]([C:23]([NH2:25])=[O:24])[CH:13]=[N:12][N:11]3[CH:26]=2)[CH:5]=[N:4]1)[CH3:2].C(O)(C(F)(F)F)=O.Br[C:35]1[CH:42]=[CH:41][C:38]([C:39]#[N:40])=[CH:37][N:36]=1.CCN(C(C)C)C(C)C>CN(C=O)C>[C:39]([C:38]1[CH:41]=[CH:42][C:35]([N:19]2[CH2:20][C@H:21]([CH3:22])[C@H:17]([NH:16][C:15]3[C:10]4[N:11]([CH:26]=[C:8]([C:6]5[CH:5]=[N:4][N:3]([CH2:1][CH3:2])[CH:7]=5)[N:9]=4)[N:12]=[CH:13][C:14]=3[C:23]([NH2:25])=[O:24])[CH2:18]2)=[N:36][CH:37]=1)#[N:40]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 50057186-Bromopyridine-3-carbonitrileHCID 89995495HCID 89995495, compound

Product 1

HCID 89995491HCID 89995491, compoundYield 63.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 2-(1-ethyl-1H-pyrazol-4-yl)-8-(((3S,4S)-4-methylpyrrolidin-3-yl)amino)imidazo[1,2-b]pyridazine-7-carboxamide, 2 TFA (0.020 g, 0.034 mmol), 6-bromonicotinonitrile (0.013 g, 0.069 mmol) and Hunig's Base (0.030 ml, 0.172 mmol) in DMF (0.3 ml) in a reaction vial was stirred at 100° C. for 5 h. 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 1 (10.0 mg, 0.022 mmol, 63.8% yield). 1H NMR (500 MHz, deuterated 1:1 methanol:chloroform) δ 8.53 (br. s., 1H), 8.51 (s, 1H), 8.15 (s, 1H), 8.11 (s, 1H), 8.07 (s, 1H), 7.84 (d, J=8.9 Hz, 1H), 6.69 (d, J=7.4 Hz, 1H), 6.32 (br. s., 1H), 4.43 (q, J=7.3 Hz, 3H), 4.19 (br. s., 1H), 4.12-3.91 (m, 2H), 3.70-3.57 (m, 1H), 3.06 (d, J=12.9 Hz, 1H), 1.72 (t, J=7.4 Hz, 3H), 1.43 (d, J=6.9 Hz, 3H). LC/MS (Method F): m/z 456.20 ([M+H]+), Rt. 1.310 min.

Workup

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

Sources & evidence

ORD record
ord-5b6d036eea264f4c85a465c5abb50006
Source dataset
uspto-grants-2016_08
Patent number
US09428511B2

Reaction notes

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