2,3-Dichloro-5,6-dicyano-1,4-benzoquinone → 4-Methyl-2-pyridin-2-yl-pyrimidine-5-carboxylic acid (5-fluoro-3-formyl-indol-1-yl)-amide

HRID 2382049Notes

Reaction equation

HRID 2382049 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([NH:11][C:12]([C:14]1[C:15]([CH3:26])=[N:16][C:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=3)=[N:18][CH:19]=1)=[O:13])[CH:6]=[CH:5]2.C(C1C(=O)C(Cl)=C(Cl)[C:31](=[O:32])C=1C#N)#N>O.CCOC(C)=O>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([NH:11][C:12]([C:14]1[C:15]([CH3:26])=[N:16][C:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=3)=[N:18][CH:19]=1)=[O:13])[CH:6]=[C:5]2[CH:31]=[O:32]

Participants

5

Reactant 2

HCID 67752,3-Dichloro-5,6-dicyano-1,4-benzoquinoneHCID 591999524-Methyl-2-pyridin-2-yl-pyrimidine-5-carboxylic acid (5-fluoro-indol-1-yl)-amide

Product 1

HCID 592000434-Methyl-2-pyridin-2-yl-pyrimidine-5-carboxylic acid (5-fluoro-3-formyl-indol-1-yl)-amideYield 43%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

A solution of 4-methyl-2-pyridin-2-yl-pyrimidine-5-carboxylic acid (5-fluoro-indol-1-yl)-amide (250 mg, 0.55 mmol) in H2O (5.5 mL) is treated with DDQ (369 mg, 1.6 mmol) in EtOAc (0.5 mL), and stirred at rt for 2 h. The mixture is diluted with EtOAc (50 mL), washed with brine (50 mL), and extracted with saturated aqueous NaHCO3 (3×50 mL). The aqueous layer is acidified to pH 2 with HCl (conc.) and washed with Et2O (50 mL). The aqueous layer is neutralized with 10% aqueous NaOH and extracted with EtOAc (3×50 mL). The combined organic layer is dried (Na2SO4), filtered and concentrated in vacuo. The residue is purified by triturating in Et2O to afford 4-methyl-2-pyridin-2-yl-pyrimidine-5-carboxylic acid (5-fluoro-3-formyl-indol-1-yl)-amide (87 mg, 43%). MS: 376 (M+H); 1H NMR (300 MHz, DMSO-d6): δ 12.53 (s, NH, 1H), 10.00 (s, 1H), 9.34 (m, 1H), 8.81 (m, 1H), 8.66 (s, 1H), 8.48 (m, 1H), 8.04 (m, 1H), 7.86 (m, 1H), 7.72 (m, 1H), 7.61 (m, 1H), 7.27 (m, 1H), 2.80 (s, 3H).

Workup

  1. washwashed with brine (50 mL)
  2. extractionextracted with saturated aqueous NaHCO3 (3×50 mL)
  3. washwashed with Et2O (50 mL)
  4. extractionextracted with EtOAc (3×50 mL)
  5. dry with materialThe combined organic layer is dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue is purified
  9. customby triturating in Et2O

Sources & evidence

ORD record
ord-015cf90d47914abfbe7a708cecc2cb5a
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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