Hydrochloric Acid → HCID 90416836, compound

HRID 633578Notes

Reaction equation

HRID 633578 reaction equation
[CH:1]1([CH2:4][O:5][C:6]2[C:14]([C:15]3[C:23]4[C:18](=[C:19]([O:24]C)[N:20]=[CH:21][CH:22]=4)[N:17]([CH3:26])[CH:16]=3)=[C:13]3[C:9]([CH:10]=[CH:11][NH:12]3)=[CH:8][CH:7]=2)[CH2:3][CH2:2]1.Cl.C(=O)(O)[O-].[Na+]>O1CCOCC1>[CH:1]1([CH2:4][O:5][C:6]2[C:14]([C:15]3[C:23]4[CH:22]=[CH:21][NH:20][C:19](=[O:24])[C:18]=4[N:17]([CH3:26])[CH:16]=3)=[C:13]3[C:9]([CH:10]=[CH:11][NH:12]3)=[CH:8][CH:7]=2)[CH2:2][CH2:3]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 90416477HCID 90416477, compound

Product 1

HCID 90416836HCID 90416836, compoundYield 7.6%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
75 °C

Procedure

A mixture of Example 98C (0.09 g, 0.26 mmol) in dioxane (5.2 mL) was treated with hydrogen chloride (4M in dioxane) (6.5 mL, 26 mmol) and heated at 75° C. for 30 minutes. The reaction mixture was neutralized with saturated sodium bicarbonate solution. The resulting mixture was partitioned between ethyl acetate and water. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered, and concentrated. The residue was purified by flash chromatography (silica gel, 0 to 20% methanol in dichloromethane). The material was further purified by reverse phase HPLC (C18, CH3CN/water (0.1% TFA), 10-80%) to provide the title compound (0.0066 g, 7.6%). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.81 (d, J=4.88 Hz, 1H), 10.38 (s, 1H), 7.41 (m, 2H), 7.12 (t, J=2.75 Hz, 1H), 6.86 (d, J=8.54 Hz, 1H), 6.80 (dd, J=6.71, 5.80 Hz, 1H), 6.37 (dd, J=3.05, 1.83 Hz, 1H), 6.14 (m, 1H), 4.15 (s, 3H), 3.74 (d, J=6.71 Hz, 2H), 1.03 (m, 1H), 0.40 (ddd, J=8.09, 5.95, 4.27 Hz, 2H), 0.15 (ddd, J=5.95, 4.58, 4.43 Hz, 2H). MS (ESI+) m/z 334.1 (M+H)+.

Workup

  1. customThe resulting mixture was partitioned between ethyl acetate and water
  2. washThe organic layer was washed with saturated aqueous sodium chloride
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography (silica gel, 0 to 20% methanol in dichloromethane)
  7. customThe material was further purified by reverse phase HPLC (C18, CH3CN/water (0.1% TFA), 10-80%)

Sources & evidence

ORD record
ord-f22d4705f2084c96af1b3486d8134ba9
Source dataset
uspto-grants-2016_04
Patent number
US09321764B2

Reaction notes

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