Methyl iodide → HCID 90465998, compound

HRID 928549Notes

Reaction equation

HRID 928549 reaction equation
[CH3:1][C:2]1[C:6]([C:7]2[C:15]3[O:16][CH2:17][CH:18]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=4)[N:13]4[C:14]=3[C:10]([C:11](=[O:25])[NH:12]4)=[CH:9][CH:8]=2)=[C:5]([CH3:26])[O:4][N:3]=1.[C:27](=O)([O-])[O-].[K+].[K+].CI>CN(C)C=O>[CH3:1][C:2]1[C:6]([C:7]2[C:15]3[O:16][CH2:17][CH:18]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=4)[N:13]4[C:14]=3[C:10]([C:11]([O:25][CH3:27])=[N:12]4)=[CH:9][CH:8]=2)=[C:5]([CH3:26])[O:4][N:3]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 90465996HCID 90465996, compound

Product 1

HCID 90465998HCID 90465998, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 9-(3,5-dimethylisoxazol-4-yl)-3-pyridin-2-yl-2,3-dihydro[1,4]oxazino[2,3,4-hi]indazol-6(5H)-one (0.03 g, 0.086 mmol) in N,N-dimethylformamide (0.24 mL) at 0° C. was treated with potassium carbonate (0.024 g, 0.172 mmol) followed by dropwise addition of 0.2 M methyl iodide in N,N-dimethylformamide (0.517 mL, 0.103 mmol) and stirred at 0° C. for 30 min. The ice bath was removed and the reaction mixture was stirred for 1 h. The reaction mixture was treated with water (20 mL) and extracted with EtOAc (30 mL). The organic layer was separated and washed with brine (10 mL), dried over sodium sulfate, filtered, and concentrated to give a colorless residue. Purification by preparative LCMS (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 30 mL/min) gave Example 6 (10 mg, 30%, first peak to elute) and Example 7 (8 mg, 20%, second peak to elute). Example 6: 1H NMR (500 MHz, DMSO-d6) δ 8.47 (d, J=4.4 Hz, 1H), 7.86-7.71 (m, 1H), 7.38-7.29 (m, 1H), 7.29-7.21 (m, 2H), 7.00 (d, J=8.0 Hz, 1H), 5.14 (dd, J=3.4 Hz, 1H), 4.93 (d, J=3.5 Hz, 2H), 3.08 (s, 3H), 2.30 (s, 3H), 2.13 (s, 3H); LCMS calculated for C20H19N4O3 (M+H)+: m/z=363.1. found: 363.1. Example 7: 1H NMR (500 MHz, DMSO-d6) δ 8.55 (d, J=4.1 Hz, 1H), 7.82-7.68 (m, 1H), 7.33 (dd, J=7.0, 5.2 Hz, 1H), 7.27 (d, J=8.3 Hz, 1H), 6.91 (d, J=8.3 Hz, 1H), 6.82 (d, J=7.9 Hz, 1H), 5.76-5.66 (m, 1H), 4.93-4.73 (m, 2H), 3.99 (s, 3H), 2.27 (s, 3H), 2.11 (s, 3H); LCMS calculated for C20H19N4O3 (M+H)+: m/z=363.1. found: 363.1.

Workup

  1. customThe ice bath was removed
  2. stirringthe reaction mixture was stirred for 1 h
  3. additionThe reaction mixture was treated with water (20 mL)
  4. extractionextracted with EtOAc (30 mL)
  5. customThe organic layer was separated
  6. washwashed with brine (10 mL)
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto give a colorless residue
  11. customPurification by preparative LCMS (XBridge C18 column
  12. washeluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 30 mL/min)
  13. customgave
  14. washExample 6 (10 mg, 30%, first peak to elute) and Example 7 (8 mg, 20%, second peak to elute)

Sources & evidence

ORD record
ord-a3340ba6a11b4e1b91b8be7fc17b4662
Source dataset
uspto-grants-2016_03
Patent number
US09290514B2

Reaction notes

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