Trifluoroacetic acid → HCID 70982784, compound

HRID 716199Notes

Reaction equation

HRID 716199 reaction equation
[NH2:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][C:9]=2[NH:14][C:15]2[N:19]3[N:20]=[C:21]([C:24]4[C:29]([F:30])=[CH:28][CH:27]=[CH:26][N:25]=4)[CH:22]=[CH:23][C:18]3=[CH:17][N:16]=2)[C@H:3]1[CH3:31].FC1C=CC=C(F)C=1C1C=CC2N(C(NC3C=NC=CC=3N3CCCC(NC(=O)OC(C)(C)C)C3C)=NC=2)N=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:1][C@H:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][C:9]=2[NH:14][C:15]2[N:19]3[N:20]=[C:21]([C:24]4[C:29]([F:30])=[CH:28][CH:27]=[CH:26][N:25]=4)[CH:22]=[CH:23][C:18]3=[CH:17][N:16]=2)[C@H:3]1[CH3:31]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 90311129HCID 90311129, compoundHCID 123544972HCID 123544972, compound

Product 1

HCID 70982784HCID 70982784, compoundYield 96%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

N-(4-((trans)-3-amino-2-methyl-1-piperidinyl)-3-pyridinyl)-2-(3-fluoro-2-pyridinyl)imidazo[1,5-b]pyridazin-7-amine (enantiomer 1) (Example 54). tert-Butyl (1-(3-((2-(2,6-difluorophenyl)imidazo[1,5-b]pyridazin-7-yl)amino)pyridin-4-yl)-2-methylpiperidin-3-yl)carbamate (first eluting enantiomer) (53 mg, 0.09 mmol) in 2 mL of DCM was treated with 0.5 mL of TFA and stirred at RT for 1 h. Volatiles were removed under reduced pressure. The residue was treated with 10 mL of 1 N NaOH, and the mixture was extracted with 3×15 mL of EtOAc. The combined organic extracts were washed with 2×5 mL of water followed by 2×5 mL of brine, dried over sodium sulfate and concentrated to give the title compound (39 mg, 96% yield) as an orange amorphous solid. MS (ESI, pos. ion) m/z: 436.1 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.47 (1 H, s), 8.00-8.17 (2 H, m), 7.63 (1 H, tt, J=8.5, 6.5 Hz), 7.39 (1 H, s), 7.30 (2 H, m), 7.16 (1 H, d, J=5.1 Hz), 6.70 (1 H, d, J=9.4 Hz), 3.37 (3 H, br.), 2.78 (2 H, m), 2.56 (1 H, m), 2.36 (1 H, m), 1.76 (1 H, m), 1.59 (2 H, m), 1.23 (1 H, m), 0.84 (3 H, d, J=6.3 Hz). 19F NMR (376 MHz, DMSO-d6) δ ppm −113.35. The relative stereochemistry was confirmed by 1H-NMR studies.

Workup

  1. customVolatiles were removed under reduced pressure
  2. additionThe residue was treated with 10 mL of 1 N NaOH
  3. extractionthe mixture was extracted with 3×15 mL of EtOAc
  4. washThe combined organic extracts were washed with 2×5 mL of water
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-9c04a84b30f84c2cbd9a8d1050014626
Source dataset
uspto-grants-2015_11
Patent number
US09187486B2

Reaction notes

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