Hydrochloric Acid → 4-(3-Amino-6-benzyloxy-7-methoxyquinoline-4-carbonyl)benzonitrile

HRID 2404230Notes

Reaction equation

HRID 2404230 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][C:18]=1[O:19][CH3:20])[N:15]=[CH:14][C:13]([N+:21]([O-])=O)=[C:12]2[C:24]([C:26]1[CH:33]=[CH:32][C:29]([C:30]#[N:31])=[CH:28][CH:27]=1)=[O:25])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl>CO.C(OCC)(=O)C.[Fe]>[NH2:21][C:13]1[CH:14]=[N:15][C:16]2[C:11]([C:12]=1[C:24]([C:26]1[CH:27]=[CH:28][C:29]([C:30]#[N:31])=[CH:32][CH:33]=1)=[O:25])=[CH:10][C:9]([O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[C:18]([O:19][CH3:20])[CH:17]=2

Participants

6

Reactant 2

HCID 313Hydrochloric AcidHCID 666328844-(6-Benzyloxy-7-methoxy-3-nitroquinoline-4-carbonyl)benzonitrile

Product 1

HCID 666325404-(3-Amino-6-benzyloxy-7-methoxyquinoline-4-carbonyl)benzonitrileYield 70.9%

Reagents, catalysts & solvents 3

HCID 23925IronCatalystHCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
66 °C

Procedure

4-(6-Benzyloxy-7-methoxy-3-nitroquinoline-4-carbonyl)benzonitrile (8.82 g, 20.07 mmol), iron powder (11.21 g, 200.7 mmol) and 2.0 M hydrochloric acid (22.76 ml) are suspended in methanol (455 ml) (stirrer motor) and heated at 66° C. for 18 h. When the reaction is complete (TLC (HPTLC) monitoring), the solid material is filtered off through kieselguhr with suction and rinsed with tetrahydrofuran (500 ml). The filtrate is evaporated to half its volume in vacuo. Semi-saturated NaCl solution (300 ml) is subsequently added, and the mixture is extracted twice with ethyl acetate (300 ml each time). The combined organic phases are dried over sodium sulfate, filtered with suction and evaporated to dryness in vacuo. The residue obtained is dissolved in ethyl acetate and filtered through a little flash silica gel. The filtrate is evaporated in vacuo, the residue is suspended in ethyl acetate (70 ml) and ethanol (20 ml), subsequently filtered off with suction and dried in a high vacuum, giving 4-(3-amino-6-benzyloxy-7-methoxyquinoline-4-carbonyl)benzonitrile (5.83 g, 14.23 mmol) as a solid having a melting point of 192.6° C. MS: 410.1 (M+H+), TLC (HPTLC): Rf=0.36 (ethyl acetate).

Workup

  1. filtrationthe solid material is filtered off through kieselguhr with suction
  2. washrinsed with tetrahydrofuran (500 ml)
  3. customThe filtrate is evaporated to half its volume in vacuo
  4. additionSemi-saturated NaCl solution (300 ml) is subsequently added
  5. extractionthe mixture is extracted twice with ethyl acetate (300 ml each time)
  6. dry with materialThe combined organic phases are dried over sodium sulfate
  7. filtrationfiltered with suction
  8. customevaporated to dryness in vacuo
  9. customThe residue obtained
  10. filtrationfiltered through a little flash silica gel
  11. customThe filtrate is evaporated in vacuo
  12. filtrationethanol (20 ml), subsequently filtered off with suction
  13. customdried in a high vacuum

Sources & evidence

ORD record
ord-64eb0f1bf88d413282ac1e8d631a57b9
Source dataset
uspto-grants-2014_08
Patent number
US08802712B2

Reaction notes

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