Hydrochloric Acid → Methyl 6-cyano-7-(4-(8-methoxyquinolin-3-ylcarbamoyl)phenoxy)chroman-4-carboxylate

HRID 1626395Notes

Reaction equation

HRID 1626395 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][C:14]1[CH:22]=[CH:21][C:17]([C:18](O)=[O:19])=[CH:16][CH:15]=1)[O:9][CH2:8][CH2:7][CH:6]2[C:23]([O:25][CH3:26])=[O:24])#[N:2].[CH3:27][O:28][C:29]1[CH:30]=[CH:31][CH:32]=[C:33]2[C:38]=1[N:37]=[CH:36][C:35]([NH2:39])=[CH:34]2.C1C=NC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>CN(C=O)C.O>[C:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][C:14]1[CH:15]=[CH:16][C:17]([C:18](=[O:19])[NH:39][C:35]3[CH:36]=[N:37][C:38]4[C:33]([CH:34]=3)=[CH:32][CH:31]=[CH:30][C:29]=4[O:28][CH3:27])=[CH:21][CH:22]=1)[O:9][CH2:8][CH2:7][CH:6]2[C:23]([O:25][CH3:26])=[O:24])#[N:2]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 181649HOAtHCID 189450658-Methoxyquinolin-3-amineHCID 462211084-(6-Cyano-4-(methoxycarbonyl)-chroman-7-yloxy)benzoic acid

Product 1

HCID 67289723Methyl 6-cyano-7-(4-(8-methoxyquinolin-3-ylcarbamoyl)phenoxy)chroman-4-carboxylateYield 42%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Dissolved 4-(6-cyano-4-(methoxycarbonyl)chroman-7-yloxy)benzoic acid (0.10 g, 0.29 mmol), 8-methoxyquinolin-3-amine (0.050 g, 0.29 mmol), and HOAT (0.039 g, 0.29 mmol) in dry DMF (1 mL) at ambient temperature. EDCI (0.049 g, 0.32 mmol) was added and the mixture stirred at ambient temperature overnight. The reaction was diluted with excess water, acidified with 10% HCl and extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and concentrated. The crude material was purified by silica gel column chromatography eluting with 2-5% methanol/dichloromethane to provide the desired product (0.061 g, 42%) as a colorless foam.

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialThe combined organic layers were dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude material was purified by silica gel column chromatography
  6. washeluting with 2-5% methanol/dichloromethane

Sources & evidence

ORD record
ord-3f4a4b17c6094a8392b5ebd647886d50
Source dataset
uspto-grants-2014_07
Patent number
US08785445B2

Reaction notes

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