Trifluoroacetic acid → HCID 90003392, compound

HRID 1487327Notes

Reaction equation

HRID 1487327 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]([CH2:22][CH3:23])[CH2:20][NH:19][CH2:18]4)=[C:14]([C:24]([NH2:26])=[O:25])[CH:13]=[N:12][N:11]3[CH:27]=2)[CH:5]=[N:4]1)[CH3:2].C(O)(C(F)(F)F)=O.[C:35](C1(C(O)=O)CC1)#[N:36].CN(C(ON1N=N[C:53]2[CH:54]=[CH:55][CH:56]=[N:57][C:52]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[C:35]([C:53]1[CH:54]=[CH:55][C:56]([N:19]2[CH2:20][C@H:21]([CH2:22][CH3:23])[C@H:17]([NH:16][C:15]3[C:10]4[N:11]([CH:27]=[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:24]([NH2:26])=[O:25])[CH2:18]2)=[N:57][CH:52]=1)#[N:36]

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 27332591-Cyanocyclopropanecarboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 89995500HCID 89995500, compound

Product 1

HCID 90003392HCID 90003392, compoundYield 76%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 2-(1-ethyl-1H-pyrazol-4-yl)-8-(((3S,4S)-4-ethylpyrrolidin-3-yl)amino)imidazo[1,2-b]pyridazine-7-carboxamide, TFA (11 mg, 0.023 mmol), 1-cyanocyclopropanecarboxylic acid (5.07 mg, 0.046 mmol), HATU (13.00 mg, 0.034 mmol) and DIPEA (0.020 ml, 0.114 mmol) in DMF (0.4 ml) was stirred at room temperature for 45 min. The crude material was purified via preparative LC/MS (preparative LC/MS Method A). Fractions containing the desired product were combined and dried via centrifugal evaporation to afford the title compound of Example 36 (8 mg, 0.017 mmol, 76% yield). 1H NMR (500 MHz, methanol-d4, 2 rotamers) δ 8.52 (d, J=7.4 Hz, 2H), 8.17 (s, 1H), 8.12 (d, J=2.5 Hz, 2H), 8.10 (s, 1H), 8.05 (d, J=5.0 Hz, 2H), 6.20 (t, J=4.2 Hz, 1H), 6.19-6.16 (m, 1H), 4.57 (dd, J=11.4, 5.0 Hz, 1H), 4.51-4.46 (m, 1H), 4.45-4.38 (m, 6H), 4.07-4.02 (m, 2H), 3.97 (t, J=10.9 Hz, 1H), 3.59 (t, J=11.4 Hz, 1H), 2.84-2.75 (m, 1H), 2.73-2.65 (m, 1H), 2.03-1.98 (m, 1H), 1.96-1.81 (m, 4H), 1.81-1.73 (m, 4H), 1.73-1.63 (m, 8H), 1.62-1.58 (m, 1H), 1.21 (t, J=7.4 Hz, 3H), 1.18 (t, J=7.4 Hz, 3H). HPLC/LCMS (Method F): m/z 461.20 ([M+H]+), Rt. 1.30 min.

Workup

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

Sources & evidence

ORD record
ord-3d566b0cc6c64e568c2d156397ff4a84
Source dataset
uspto-grants-2016_08
Patent number
US09428511B2

Reaction notes

Loading…