Acetic Acid → HCID 9885873, compound

HRID 456921Notes

Reaction equation

HRID 456921 reaction equation
[C:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][C:8]([C:13]1[C:14](=[O:23])[NH:15][C:16]3[C:21]([CH:22]=1)=[CH:20][CH:19]=[CH:18][CH:17]=3)=[CH:7]2)(=O)[CH3:2].[NH:24]1[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.C(O)(=O)C.C([BH3-])#N.[Na+]>CO.O1CCOCC1>[N:24]1([CH:1]([C:4]2[CH:5]=[C:6]3[C:10](=[CH:11][CH:12]=2)[NH:9][C:8]([C:13]2[C:14](=[O:23])[NH:15][C:16]4[C:21]([CH:22]=2)=[CH:20][CH:19]=[CH:18][CH:17]=4)=[CH:7]3)[CH3:2])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1

Participants

7

Reactant 4

HCID 176Acetic Acid2×HCID 8083Morpholine2×HCID 5003444Sodium cyanoborohydride2×HCID 22668268HCID 22668268, compound

Product 1

HCID 9885873HCID 9885873, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 3-(5-acetyl-1H-indol-2-yl)-2(1H)-quinolinone (8-4, 50.0 mg, 0.165 mmol, 1 equiv), morpholine (0.070 mL, 0.83 mmol, 5.0 equiv), acetic acid (0.050 mL, 0.83 mmol, 5.0 equiv), sodium cyanoborohydride (52 mg, 0.83 mmol, 5.0 equiv), and activated powdered 3 angstrom molecular sieves in anhydrous 20% dioxane in methanol (15 mL) was heated at 50° C. for 8 hours. Additional morpholine (0.070 mL, 0.83 mmol, 5.0 equiv), acetic acid (0.050 mL, 0.83 mmol, 5.0 equiv), and sodium cyanoborohydride (52 mg, 0.83 mmol, 5.0 equiv) was added, and this was repeated (3×) every 8–12 hours over the course of two days. The reaction mixture was partitioned between a 1:1 mixture of saturated sodium carbonate solution and brine and ethyl acetate (100 mL). The organic layer was dried over sodium sulfate and concentrated. The residue was purified by reverse-phase liquid chromatography (H2O/CH3CN gradient w/0.1% TFA present) to provide 3-{5-[1-(4-morpholinyl) ethyl]-1H-indol-2-yl}-2(1H)quinolinone (8-5) as a yellow solid. 1H NMR (500 MHz, CDCl3) δ 11.15 (s, 1H), 9.28 (br s, 1H), 8.37 (s, 1H), 7.72 (d, 1H, J=8.0 Hz), 7.57 (s, 1H), 7.54 (br t, 1H, J=7.6 Hz), 7.43 (d, 1H, J=8.0 Hz), 7.32 (t, 1H, J=7.6 Hz), 7.27 (d, 1H, J=7.8 Hz), 7.22 (d, 1H, J=7.9 Hz), 7.04 (s, 1H), 3.72 (m, 4H), 3.41 (q, 1H, J=6.6 Hz), 2.56 (m, 2H), 2.43 (m, 2H), 1.46 (d, 3H, J=6.6 Hz).

Workup

  1. customevery 8–12 hours
  2. customover the course of two days
  3. customThe reaction mixture was partitioned between a 1:1 mixture of saturated sodium carbonate solution and brine and ethyl acetate (100 mL)
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified by reverse-phase liquid chromatography (H2O/CH3CN gradient w/0.1% TFA present)

Sources & evidence

ORD record
ord-594de455066946a1bbbe0974e869d8a4
Source dataset
uspto-grants-2007_03
Patent number
US07186723B2

Reaction notes

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