Methyl 3-indoleglyoxylate → HCID 11582121, compound

HRID 2262662Notes

Reaction equation

HRID 2262662 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]2)=[CH:4][C:3]=1[CH2:15][C:16]([NH2:18])=[O:17].C[O:20][C:21](=O)[C:22]([C:24]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[NH:26][CH:25]=1)=O.CC([O-])(C)C.[K+]>C1COCC1>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]2)=[CH:4][C:3]=1[C:15]1[C:16](=[O:17])[NH:18][C:21](=[O:20])[C:22]=1[C:24]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[NH:26][CH:25]=1

Participants

5

Reactant 3

HCID 588944Methyl 3-indoleglyoxylateHCID 23665647Potassium tert-butoxideHCID 68684908HCID 68684908, compound

Product 1

HCID 11582121HCID 11582121, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 2-[2-amino-5-(4-methyl-piperazin-1-yl)-phenyl]-acetamide (124 mg, 0.50 mmol) and (1H-indol-3-yl)-oxo-acetic acid methyl ester (183 mg, 0.90 mmol) in dry THF (4.0 mL) is added a solution of 1.0 M t-BuOK in THF (2.0 mL, 2.0 mmol) at 0° C. under argon. After stirring for 30 min at 0° C. and 30 min at RT, TLC indicates the complete consumption of the acetamide. The 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. Red solid. 1H NMR (DMSO-d6, 400 MHz): δ 1.70 (s, 9H, CH3COO−), 2.25 (s, 3H), 2.22-2.38 (m, 4H), 2.78-2.84 (m, 4H), 6.51 (d, J=8.7 Hz, 1H), 6.63 (d, J=2.8 Hz, 1H), 6.64-6.68 (m, 2H), 6.77 (dd, J=8.7 Hz, J=2.8 Hz, 1H), 6.97-7.02 (m, 1H), 7.35 (d, J=8.0 Hz, 1H), 7.90 (s, 1H), 11.91 (bs, 1H). ES+-MS: 402 [M+H]+.

Workup

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

Sources & evidence

ORD record
ord-17fa8ce67aa04bc380c6dc9b5a71ec14
Source dataset
uspto-grants-2010_12
Patent number
US07851475B2

Reaction notes

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