2,3-Dichloro-5,6-dicyano-1,4-benzoquinone → 3-Ethyl 5-methyl 2-amino-4-(chroman-6-yl)-6-methylpyridine-3,5-dicarboxylate

HRID 1912542Notes

Reaction equation

HRID 1912542 reaction equation
[NH2:1][C:2]1[NH:3][C:4]([CH3:27])=[C:5]([C:23]([O:25][CH3:26])=[O:24])[CH:6]([C:13]2[CH:14]=[C:15]3[C:20](=[CH:21][CH:22]=2)[O:19][CH2:18][CH2:17][CH2:16]3)[C:7]=1[C:8]([O:10][CH2:11][CH3:12])=[O:9].C(C1C(=O)C(Cl)=C(Cl)C(=O)C=1C#N)#N>ClCCl>[NH2:1][C:2]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[C:6]([C:13]2[CH:14]=[C:15]3[C:20](=[CH:21][CH:22]=2)[O:19][CH2:18][CH2:17][CH2:16]3)[C:5]([C:23]([O:25][CH3:26])=[O:24])=[C:4]([CH3:27])[N:3]=1

Participants

4

Reactant 2

HCID 67752,3-Dichloro-5,6-dicyano-1,4-benzoquinoneHCID 712088353-Ethyl 5-methyl 2-amino-4-(chroman-6-yl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate

Product 1

HCID 712092193-Ethyl 5-methyl 2-amino-4-(chroman-6-yl)-6-methylpyridine-3,5-dicarboxylateYield 64.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of methyl 2-(chroman-6-ylmethylene)-3-oxobutanoate (8.27 g, 31.8 mmol), ethyl 3,3-diaminoacrylate, hydrochloride (5.29 g, 31.8 mmol) and 4-methylmorpholine (3.49 mL, 31.8 mmol) in Isopropanol (76.0 mL) was heated to 90° C. overnight. The mixture was concentrated, dissolved in ethyl acetate, washed with brine, dried over sodium sulfate, filtered and concentrated to provide crude 3-ethyl 5-methyl 2-amino-4-(chroman-6-yl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate which was used without further purification. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.00-6.87 (m, 3 H), 6.64-6.58 (m, 1 H), 6.20 (br. s., 2 H), 4.83-4.77 (m, 1 H), 4.15-4.05 (m, 4 H), 3.71-3.63 (m, 3 H), 2.71 (t, J=6.3 Hz, 2 H), 2.27-2.16 (m, 3 H), 1.99-1.93 (m, 2 H), 1.27-1.22 (m, 3 H); LC/MS (m/z) ES+=373.3 (M+1). A solution of crude 3-ethyl 5-methyl 2-amino-4-(chroman-6-yl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate in dichloromethane (DCM) (216 mL) was treated with DDQ (7.22 g, 31.8 mmol) and then stirred at ambient temperature (mixture turned dark within one minute). The mixture was filtered over Celite™. The filtrate was diluted with saturated sodium bicarbonate and the layers were separated. The aqueous phase was extracted with DCM. The combined extracts were washed with brine, dried over sodium sulfate, filtered and concentrated. The residue was purified on silica gel (0-100% hexane/EA) to afford 3-ethyl 5-methyl 2-amino-4-(chroman-6-yl)-6-methylpyridine-3,5-dicarboxylate (7.64 g, 20.63 mmol, 64.9% yield) as a brown solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 6.86 (d, 1 H), 6.81 (s, 1 H), 6.73 (d, J=8.4 Hz, 1 H), 6.23-6.02 (m, 2 H), 4.17 (t, J=4.7 Hz, 2 H), 3.99-3.77 (m, 2 H), 3.52-3.43 (m, 3 H), 2.73 (br. s., 2H), 2.45-2.35 (m, 3 H), 1.98 (br. s., 2 H), 0.83-0.67 (m, 3 H); LC/MS (m/z) ES+=371.3 (M+1).

Workup

  1. customwas used without further purification
  2. filtrationThe mixture was filtered over Celite™
  3. additionThe filtrate was diluted with saturated sodium bicarbonate
  4. customthe layers were separated
  5. extractionThe aqueous phase was extracted with DCM
  6. washThe combined extracts were washed with brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified on silica gel (0-100% hexane/EA)

Sources & evidence

ORD record
ord-2b402777a9794ad5a1f7a344d9bf953e
Source dataset
uspto-grants-2013_12
Patent number
US08609653B2

Reaction notes

Loading…