Methyl 3-indoleglyoxylate → HCID 11539514, compound

HRID 2262664Notes

Reaction equation

HRID 2262664 reaction equation
[C:1]([NH:4][C:5]1[CH:10]=[CH:9][C:8]([N:11]2[CH2:16][CH2:15][N:14]([CH3:17])[CH2:13][CH2:12]2)=[CH:7][C:6]=1[CH2:18][C:19]([NH2:21])=[O:20])(=[O:3])[CH3:2].C[O:23][C:24](=O)[C:25]([C:27]1[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[NH:29][CH:28]=1)=O.CC([O-])(C)C.[K+]>C1COCC1>[NH:29]1[C:30]2[C:35](=[CH:34][CH:33]=[CH:32][CH:31]=2)[C:27]([C:25]2[C:24](=[O:23])[NH:21][C:19](=[O:20])[C:18]=2[C:6]2[CH:7]=[C:8]([N:11]3[CH2:12][CH2:13][N:14]([CH3:17])[CH2:15][CH2:16]3)[CH:9]=[CH:10][C:5]=2[NH:4][C:1](=[O:3])[CH3:2])=[CH:28]1

Participants

5

Reactant 3

HCID 588944Methyl 3-indoleglyoxylateHCID 23665647Potassium tert-butoxideHCID 68685144HCID 68685144, compound

Product 1

HCID 11539514HCID 11539514, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of 2-[2-Acetylamino-5-(4-methyl-piperazin-1-yl)-phenyl]-acetamide (145 mg, 0.50 mmol) and (1H-indol-3-yl)-oxo-acetic acid methyl ester (183 mg, 0.90 mmol) in dry THF (6.0 mL) is added a solution of 1.0 M t-BuOK in THF (2.0 mL, 2.0 mmol) at 0° C. under argon. The resulting yellow suspension is stirred for 18 h at RT. The now dark red reaction mixture is partitioned between EtOAc (25 mL) and brine (25 mL), and the layers are separated. The pH of the aqueous layer is adjusted to 6 with a sat., aqueous NH4Cl solution. The aqueous layer is extracted with EtOAc (2×25 mL) and the combined organic layers are washed with brine (25 mL), dried over Na2SO4, and concentrated at reduced pressure. The crude product is purified by FCC (EtOAc/AcOH/H2O 5.5:1:1) to afford the title compound as its water soluble acetate salt. Orange solid. 1H NMR (DMSO-de, 400 MHz): δ 1.75 (s, 12H, CH3COO), 2.16 (s, 3H), 2.31-2.38 (m, 4H), 2.92-2.99 (m, 4H), 6.61 (d, J=7.8 Hz, 1H), 6.66 (t, J=7.4 Hz, 1H), 6.75 (d, J=2.5 Hz, 1H), 6.92 (dd, J=9.0 Hz, J=2.7 Hz, 1H), 6.99 (t, J=7.5 Hz, 1H), 7.32 (d, J=8.1 Hz, 1H), 7.47 (d, J=8.9 Hz, 1H), 7.75 (s, 1H), 8.69 (s, 1H), 11.86 (bs, 1H). ES+-MS: 444 [M+H]+.

Workup

  1. customThe now dark red reaction mixture
  2. customis partitioned between EtOAc (25 mL) and brine (25 mL)
  3. customthe layers are separated
  4. extractionThe aqueous layer is extracted with EtOAc (2×25 mL)
  5. washthe combined organic layers are washed with brine (25 mL)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated at reduced pressure
  8. customThe crude product is purified by FCC (EtOAc/AcOH/H2O 5.5:1:1)

Sources & evidence

ORD record
ord-fa71c544d72f4739810c246b430c94be
Source dataset
uspto-grants-2010_12
Patent number
US07851475B2

Reaction notes

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