Dimethylformamide → HCID 178464591, compound

HRID 847165Notes

Reaction equation

HRID 847165 reaction equation
[NH2:1][C@@H:2]1[C:7]2[CH:8]=[C:9]([C:12]#[N:13])[CH:10]=[CH:11][C:6]=2[O:5][C:4]([CH3:15])([CH3:14])[C@H:3]1[OH:16].Cl.CN(C)CCC[CH2:23][CH2:24][N:25]=[C:26]=[NH:27].[CH3:29][N:30](C)C=O>>[C:29]([N:27]=[C:26]([NH:25][CH2:24][CH3:23])[NH:1][C@@H:2]1[C:7]2[CH:8]=[C:9]([C:12]#[N:13])[CH:10]=[CH:11][C:6]=2[O:5][C:4]([CH3:14])([CH3:15])[C@H:3]1[OH:16])#[N:30]

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 10943936(3S,4R)-4-amino-3-hydroxy-2,2-dimethyl-chroman-6-carbonitrileHCID 574828161-(3-Dimethylaminopropyl)-2-ethylcarbodiimide hydrochloride

Product 1

HCID 178464591HCID 178464591, compound

Procedure

To a solution of the title A compound (1.15 g, 8.9 mmol) and (trans)-4-amino-3,4-dihydro-3-hydroxy-2,2-dimethyl-2H-1-benzopyran-6-carbonitrile (prepared according to Evans et al., J. Med. Chem., 1983, 26, 1582 and J. Med. Chem., 1986, 29, 2194). (1.5 g, 6.9 mmol) in dimethylformamide (5 mL) under argon was added 1-(3-dimethylaminopropyl)-2-ethylcarbodiimide hydrochloride (1.71 g, 8.9 mmol) at room temperature. The reaction mixture was stirred at room temperature for 2 hours and then partitioned between 1N HCl and ethyl acetate. The organic phase was separated and the aqueous phase was reextracted with ethyl acetate. The combined organic phase was washed with water, aqueous sodium bicarbonate and brine. After drying over anhydrous magnesium sulfate, the solvent was evaporated and the residue was purified by flash chromatography on silica gel (25% acetone in dichloromethane). The fractions containing the desired product were combined and evaporated to yield a colorless solid (801 mg). This solid product was recrystallized from acetonitrile-ether to yield the title compound, m.p. 185°-188° C.

Workup

  1. custompartitioned between 1N HCl and ethyl acetate
  2. customThe organic phase was separated
  3. washThe combined organic phase was washed with water, aqueous sodium bicarbonate and brine
  4. dry with materialAfter drying over anhydrous magnesium sulfate
  5. customthe solvent was evaporated
  6. customthe residue was purified by flash chromatography on silica gel (25% acetone in dichloromethane)
  7. additionThe fractions containing the desired product
  8. customevaporated

Sources & evidence

ORD record
ord-cf4113ec25aa4ac48035e8c99785b160
Source dataset
uspto-grants-1992_08
Patent number
US05140031

Reaction notes

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