Diisopropylethylamine → HCID 68986781, compound

HRID 240795Notes

Reaction equation

HRID 240795 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([C:10]3[O:14][N:13]=[C:12]([C:15]([OH:17])=O)[CH:11]=3)=[CH:7][CH:8]=2)[CH:3]=[N:2]1.CN(C(ON1N=N[C:28]2[CH:29]=[CH:30][CH:31]=N[C:27]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C([N:45]([CH:48]([CH3:50])[CH3:49])CC)(C)C>CN(C)C=O>[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([C:10]3[O:14][N:13]=[C:12]([C:15]([NH:45][C@H:48]([C:49]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[CH3:50])=[O:17])[CH:11]=3)=[CH:7][CH:8]=2)[CH:3]=[N:2]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57612255HCID 57612255, compound

Product 1

HCID 68986781HCID 68986781, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent4×

Conditions

Temperature
40 °C

Procedure

5-(1H-Indazol-5-yl)isoxazole-3-carboxylic acid (36 mg, 0.16 mmol, Example 71A), was dissolved in N,N-dimethylformamide (1.0 mL) followed by the addition of HATU (60 mg, 0.16 mmol) dissolved in N,N-dimethylformamide (0.5 mL). Then a solution of(S)-1-phenylethanamine (22 mg, 0.18 mmol), dissolved in N,N-dimethylformamide (0.6 mL) was added, followed by diisopropylethylamine (56 μL, 0.32 mmol) dissolved in N,N-dimethylformamide (0.2 mL). The resulting mixture was shaken for 3 hours at 40° C. The reaction was filtered, checked by LC/MS and concentrated to dryness. The residues were dissolved in 1:1 dimethyl sulfoxide/methanol and purified by reverse phase HPLC (Phenomenex® Luna® C8(2) 5 μm 100 Å AXIA™ column (30 mm×75 mm), 50 mL/min, 10-100% acetonitrile/0.1% trifluoroacetic acid in water) to provide the title product. 1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 1.50 (d, 3H), 5.06-5.22 (m, 1H), 7.23-7.29 (m, 2H), 7.34-7.38 (m, 2H), 7.40-7.45 (m, 2H), 7.70-7.75 (m, 1H), 7.87-7.92 (m, 1H), 8.25-8.27 (m, 1H), 8.39-8.41 (m, 1H), 9.28 (d, 1H). MS (ESI+) m/z 333 (M+H)+; (ESI−) m/z 331 (M−H)−.

Workup

  1. additionwas added
  2. filtrationThe reaction was filtered
  3. concentrationconcentrated to dryness
  4. dissolutionThe residues were dissolved in 1:1 dimethyl sulfoxide/methanol
  5. custompurified by reverse phase HPLC (Phenomenex® Luna® C8(2) 5 μm 100 Å AXIA™ column (30 mm×75 mm), 50 mL/min, 10-100% acetonitrile/0.1% trifluoroacetic acid in water)

Sources & evidence

ORD record
ord-5261829738aa41538b5dfef9f8106adf
Source dataset
uspto-grants-2014_02
Patent number
US08648069B2

Reaction notes

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