1,4-Benzodioxan-6-ylamine → HCID 57326704, compound

HRID 1019659Notes

Reaction equation

HRID 1019659 reaction equation
[O:1]1[C:6]2[CH:7]=[CH:8][C:9]([NH2:11])=[CH:10][C:5]=2[O:4][CH2:3][CH2:2]1.Cl[C:13]1[N:18]=[C:17]([N:19]2[CH2:24][CH2:23][CH2:22][C@H:21]([C:25]([NH:27][CH2:28][C:29]3[CH:34]=[CH:33][C:32]([CH3:35])=[CH:31][CH:30]=3)=[O:26])[CH2:20]2)[CH:16]=[CH:15][N:14]=1>CS(C)=O>[O:1]1[CH2:2][CH2:3][O:4][C:5]2[CH:10]=[C:9]([NH:11][C:13]3[N:18]=[C:17]([N:19]4[CH2:24][CH2:23][CH2:22][C@H:21]([C:25]([NH:27][CH2:28][C:29]5[CH:30]=[CH:31][C:32]([CH3:35])=[CH:33][CH:34]=5)=[O:26])[CH2:20]4)[CH:16]=[CH:15][N:14]=3)[CH:8]=[CH:7][C:6]1=2

Participants

4

Reactant 2

HCID 891481,4-Benzodioxan-6-ylamineHCID 57326401HCID 57326401, compound

Product 1

HCID 57326704HCID 57326704, compoundYield 18%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 1,4-benzodioxan-6-amine (Sigma-Aldrich, 65.8 mg, 0.435 mmol) and (S)-1-(2-chloropyrimidin-4-yl)-N-(4-methylbenzylipiperidine-3-carboxamide (M5, 100 mg, 0.290 mmol) in DMSO (0.6 mL) was heated at 90° C. for 16 hours. The mixture was then cooled to room temperature, filtered and was purified with reversed-phase HPLC (Phenomenex Gemini-NX 10 μL 110 Å, AXIA packed column, 100×50 mm, 60 mL/min, 10-95% ACN/H2O, 0.1% TFA, 10 min gradient). After concentration of the fractions by vacuum distillation, the product was diluted with saturated aqueous NaHCO3 and extracted with DCM (3×). The combined organic layers were dried over Na2SO4, filtered and concentrated to provide the desired product in 18% yield. 1H NMR (300 MHz, CDCl3) δ ppm 1.66-1.79 (m, 2H), 1.85-2.00 (m, 1H), 2.04-2.19 (m, 1H), 2.30 (s, 3H), 2.45 (br. s., 1H), 3.24 (t, J=9.9 Hz, 1H), 3.69 (dd, J=13.7, 8.0 Hz, 1H), 3.83 (d, J=12.6 Hz, 1H), 4.12 (d, J=12.1 Hz, 1H), 4.19 (s, 4H), 4.34 (d, J=5.4 Hz, 2H), 6.00 (d, J=6.1 Hz, 1H), 6.39 (br. s., 1H), 6.76 (d, J=8.6 Hz, 1H), 6.85 (dd, J=10.7, 9.1 Hz, 1H), 6.79-6.92 (m, 1H), 7.07 (s, 4H), 7.17-7.22 (m, 1H), 7.89 (d, J=6.3 Hz, 1H); M+H 460.23367.

Workup

  1. temperatureThe mixture was then cooled to room temperature
  2. filtrationfiltered
  3. customwas purified with reversed-phase HPLC (Phenomenex Gemini-NX 10 μL 110 Å, AXIA packed column, 100×50 mm, 60 mL/min, 10-95% ACN/H2O, 0.1% TFA, 10 min gradient)
  4. distillationAfter concentration of the fractions by vacuum distillation
  5. additionthe product was diluted with saturated aqueous NaHCO3
  6. extractionextracted with DCM (3×)
  7. dry with materialThe combined organic layers were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-41a97c73692f41278dc40082bfd8e603
Source dataset
uspto-grants-2014_05
Patent number
US08716281B2

Reaction notes

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