Malononitrile → 2,7,8-triamino-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene-3-carbonitrile

HRID 2427480Notes

Reaction equation

HRID 2427480 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([O:12][CH3:13])[C:9]=1[O:10][CH3:11])[CH:5]=O.[C:14](#[N:18])[CH2:15][C:16]#[N:17].CN(C)C(C)C.[NH2:25][C:26]1[C:31]([NH2:32])=[CH:30][CH:29]=[CH:28][C:27]=1[OH:33]>C(O)C>[NH2:17][C:16]1[O:33][C:27]2[C:28]([CH:5]([C:4]3[CH:7]=[C:8]([O:12][CH3:13])[C:9]([O:10][CH3:11])=[C:2]([Br:1])[CH:3]=3)[C:15]=1[C:14]#[N:18])=[CH:29][CH:30]=[C:31]([NH2:32])[C:26]=2[NH2:25]

Participants

6

Reactant 4

HCID 8010MalononitrileHCID 70452N,N-DimethylisopropylamineHCID 813793-Bromo-4,5-dimethoxybenzaldehydeHCID 5799372,3-Diaminophenol

Product 1

HCID 102020482,7,8-triamino-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene-3-carbonitrileYield 82%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A suspension of 3-bromo-4,5-dimethoxybenzaldehyde (1500 g, 6.12 moles, 1.1 eq) and malononitrile (404 g, 6.12 moles, 1.1 eq) in ethanol 99% (12 L, 7 volumes) was stirred at room temperature under N2(g). Dimethylisopropylamine (339 mL, 2.78 moles, 0.5 eq) was added slowly (which caused an exotherm from about 14° C. to about 26° C.) and the reaction mixture was stirred at room temperature for about 2 h under N2(g). The yellow thick suspension was analyzed by HPLC to monitor the appearance of the Knoevenagel intermediate and the disappearance of the aldehyde. 2,3-Diaminophenol (690.66 g, 5.56 moles, 1 eq) was added and the reaction mixture was stirred at room temperature overnight. The resulting beige-brown suspension was filtered and the cake was washed with cold CH2Cl2 (3000 mL). The solids were dried under vacuum to give 2,7,8-triamino-4-(3-bromo-4,5-dimethoxy-phenyl)-3-cyano-4H-chromene (1.9 kg, 82% yield). 1H NMR (300 MHz) (DMSO-d6, ppm): 3.71 (s, 3H), 3.82 (s, 3H), 4.43 (s, 2H), 4.56 (s, 1H), 4.70 (s, 2H), 6.09 (d, J=8 Hz, 1H), 6.26 (d, J=8 Hz, 1H), 6.76 (s, 2H), 6.78 (d, J=2 Hz, 1H), 6.90 (d, J=2 Hz, 1H).

Workup

  1. customfrom about 14° C. to about 26° C.
  2. stirringwas stirred at room temperature for about 2 h under N2(g)
  3. stirringthe reaction mixture was stirred at room temperature overnight
  4. filtrationThe resulting beige-brown suspension was filtered
  5. washthe cake was washed with cold CH2Cl2 (3000 mL)
  6. customThe solids were dried under vacuum

Sources & evidence

ORD record
ord-731f98d1cbd84575aced6442f3b7ebff
Source dataset
uspto-grants-2011_06
Patent number
US07968595B2

Reaction notes

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