Cyclohexanemethylamine → HCID 57612513, compound

HRID 1752581Notes

Reaction equation

HRID 1752581 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=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH:42]1([CH2:48][NH2:49])[CH2:47][CH2:46][CH2:45][CH2:44][CH2:43]1.C(N(C(C)C)CC)(C)C>CN(C)C=O>[CH:42]1([CH2:48][NH:49][C:15]([C:12]2[CH:11]=[C:10]([C:6]3[CH:5]=[C:4]4[C:9](=[CH:8][CH:7]=3)[NH:1][N:2]=[CH:3]4)[O:14][N:13]=2)=[O:17])[CH2:47][CH2:46][CH2:45][CH2:44][CH2:43]1

Participants

6

Reactant 4

HCID 76688CyclohexanemethylamineHCID 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 57612513HCID 57612513, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent4×

Conditions

Temperature
40 °C

Procedure

5-(1H-Indazol-5-yl)isoxazole-3-carboxylic acid (35 mg, 0.15 mmol, Example 71A), was dissolved in N,N-dimethylformamide (0.8 mL) followed by the addition of HATU (60 mg, 0.15 mmol) dissolved in N,N-dimethylformamide (0.8 mL). Then a solution of 1-cyclohexylmethanamine (17 mg, 0.17 mmol), dissolved in N,N-dimethylformamide (0.8 mL) was added, followed by diisopropylethylamine (56 μL, 0.31 mmol) dissolved in N,N-dimethylformamide (0.8 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 100A 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 0.91-0.97 (m, 2H), 1.12-1.27 (m, 4H), 1.61-1.75 (m, 5H), 3.08-3.16 (m, 2H), 7.22-7.24 (m, 1H), 7.71-7.75 (m, 1H), 7.87-7.92 (m, 1H), 8.23-8.27 (m, 1H), 8.38-8.41 (m, 1H). MS (ESI+) m/z 325 (M+H)+; (ESI−) m/z 323 (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 100A AXIA™ column (30 mm×75 mm), 50 mL/min, 10-100% acetonitrile/0.1% trifluoroacetic acid in water)

Sources & evidence

ORD record
ord-af478fa94b3f42f1a7ca1a4ab9463dbb
Source dataset
uspto-grants-2015_10
Patent number
US09163007B2

Reaction notes

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