Hydrochloric Acid → HCID 67442431, compound

HRID 1801259Notes

Reaction equation

HRID 1801259 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[NH:11][CH:10]([C:15]1[CH:16]=[C:17]([CH:21]=[CH:22][CH:23]=1)[C:18](O)=[O:19])[C:9]([CH3:25])([CH3:24])[CH2:8]2)=[O:4].ON1C2C=CC=CC=2N=N1.CN(C)CCCN=C=NCC.Cl.C[N:49]1[CH2:54][CH2:53][O:52][CH2:51][CH2:50]1.O1CCC(N)C1>ClCCl.C(OCC)(=O)C>[CH3:24][C:9]1([CH3:25])[CH2:8][C:13]2[C:12](=[CH:7][CH:6]=[C:5]([C:3]([O:2][CH3:1])=[O:4])[CH:14]=2)[NH:11][CH:10]1[C:15]1[CH:23]=[CH:22][CH:21]=[C:17]([C:18](=[O:19])[NH:49][CH:50]2[CH2:54][CH2:53][O:52][CH2:51]2)[CH:16]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 3365553Oxolan-3-amineHCID 674419763-(6-(Methoxycarbonyl)-3,3-dimethyl-1,2,3,4-tetrahydroquinolin-2-yl)benzoic acid

Product 1

HCID 67442431HCID 67442431, compoundYield 131.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of 3-(6-(methoxycarbonyl)-3,3-dimethyl-1,2,3,4-tetrahydroquinolin-2-yl)benzoic acid (150 mg, 0.44 mmol.) in dichloromethane (10 mL) was added N-hydroxybenzotriazole (89.2 mg, 0.66 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide.hydrochloric acid (253 mg, 1.32 mmol.), followed by 4-methylmorpholine (133.5 mg, 1.32 mmol) and the resultant mixture was stirred at room temperature for 1 h. Then tetrahydrofuran-3-amine (57.5 mg, 0.66 mmol) was added to the flask and the reaction mixture was stirred under nitrogen overnight. Thin layer chromatography (petroleum ether:ethyl acetate=1:1) and LC-MS showed the reaction was complete. The reaction was quenched with water and extracted with dichloromethane (twice). The combined organic layers were washed with 2% sodium hydroxide aqueous solution (twice) and water (3 times), dried over anhydrous sodium sulfate. Removal of the solvent in vacuo gave 236 mg methyl 3,3-dimethyl-2-(3-(tetrahydrofuran-3-ylcarbamoyl)phenyl)-1,2,3,4-tetrahydroquinoline-6-carboxylate of as a white solid, which was dissolved in methanol and treated with sodium borohydride (24 mg, 0.63 mmol) for an additional 2 h. LC-MS showed the reaction was complete. The reaction was quenched with water and extracted with ethyl acetate/tetrahydrofuran, dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to afford 192 mg of desired product as a white solid, which was pure enough for next step without further purification.

Workup

  1. customThe reaction was quenched with water
  2. extractionextracted with dichloromethane (twice)
  3. washThe combined organic layers were washed with 2% sodium hydroxide aqueous solution (twice) and water (3 times)
  4. dry with materialdried over anhydrous sodium sulfate
  5. customRemoval of the solvent in vacuo

Sources & evidence

ORD record
ord-d9bf82917dbd4e9384e31fe941b2fec5
Source dataset
uspto-grants-2013_01
Patent number
US08344137B2

Reaction notes

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