Trifluoroacetic acid → HCID 89995636, compound

HRID 1487335Notes

Reaction equation

HRID 1487335 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][F: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]([C:37]1([C:40](O)=[O:41])[CH2:39][CH2:38]1)#[N:36].CN(C(ON1N=NC2C=CC=NC1=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:37]1([C:40]([N:19]2[CH2:20][C@H:21]([CH2:22][F: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)=[O:41])[CH2:39][CH2:38]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 89995502HCID 89995502, compound

Product 1

HCID 89995636HCID 89995636, compoundYield 59.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 2-(1-ethyl-1H-pyrazol-4-yl)-8-(((3S,4S)-4-(fluoromethyl)pyrrolidin-3-yl)amino)imidazo[1,2-b]pyridazine-7-carboxamide, TFA (15 mg, 0.031 mmol), 1-cyanocyclopropanecarboxylic acid (6.85 mg, 0.062 mmol), HATU (17.59 mg, 0.046 mmol) and DIPEA (0.027 ml, 0.154 mmol) in DMF (0.4 ml) in a reaction vial was stirred at room temperature for 135 min. 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 56 (8.5 mg, 59.2% yield). 1H NMR (500 MHz, DMSO-d6, two rotamers) δ 10.74 (d, J=8.9 Hz, 1H), 10.70 (d, J=8.4 Hz, 1H), 8.49 (br. s., 1H), 8.47 (br. s., 1H), 8.29 (br. s., 1H), 8.28 (br. s., 1H), 8.17 (s, 2H), 8.02 (br. s., 2H), 7.90 (s, 2H), 7.43 (br. s., 2H), 6.14 (br. s., 1H), 6.06 (br. s., 1H), 4.75 (d, J=5.4 Hz, 1H), 4.69 (d, J=6.4 Hz, 2H), 4.59 (d, J=6.9 Hz, 2H), 4.29 (dd, J=9.9, 5.9 Hz, 1H), 4.17 (q, J=7.4 Hz, 4H), 3.91-3.80 (m, 3H), 3.76 (dd, J=12.4, 8.9 Hz, 1H), 3.55 (d, J=10.9 Hz, 1H), 3.47 (dd, J=12.4, 7.4 Hz, 1H), 3.15 (dd, J=13.1, 6.2 Hz, 1H), 3.10-2.99 (m, 1H), 1.63 (br. s., 2H), 1.60-1.49 (m, 6H), 1.40 (t, J=7.2 Hz, 6H). HPLC/LCMS (Method F): m/z 466.21 ([M+H]+), Rt. 1.118 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-8a0a82f0ed614e5a8267669fb6cbde64
Source dataset
uspto-grants-2016_08
Patent number
US09428511B2

Reaction notes

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