Hydrochloric Acid → Methyl 2-(3-((1-ethylpyrrolidin-2-yl)methylcarbamoyl)phenyl)-3,3-dimethyl-1,2,3,4-tetrahydroquinoline-6-carboxylate

HRID 1801335Notes

Reaction equation

HRID 1801335 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.CN1CCOCC1.[CH2:55]([N:57]1[CH2:61][CH2:60][CH2:59][CH:58]1[CH2:62][NH2:63])[CH3:56]>ClCCl>[CH2:55]([N:57]1[CH2:61][CH2:60][CH2:59][CH:58]1[CH2:62][NH:63][C:18]([C:17]1[CH:16]=[C:15]([CH:10]2[C:9]([CH3:24])([CH3:25])[CH2:8][C:7]3[C:12](=[CH:13][CH:14]=[C:5]([C:3]([O:2][CH3:1])=[O:4])[CH:6]=3)[NH:11]2)[CH:23]=[CH:22][CH:21]=1)=[O:19])[CH3:56]

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 1172952-Aminomethyl-1-ethylpyrrolidineHCID 67441976HCID 67441976, compound

Product 1

HCID 67442755Methyl 2-(3-((1-ethylpyrrolidin-2-yl)methylcarbamoyl)phenyl)-3,3-dimethyl-1,2,3,4-tetrahydroquinoline-6-carboxylateYield 122.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of 3-(6-(methoxycarbonyl)-3,3-dimethyl-1,2,3,4-tetrahydroquinolin-2-yl)benzoic acid (100 mg, 0.29 mmol, 1.0 eq.) in dichloromethane (6.7 ml) was added N-hydroxybenzotriazole (59.7 mg, 0.44 mmol, 1.5 eq.) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide.hydrochloric acid (169.7 mg, 0.88 mmol, 3.0 eq.), followed by 4-methylmorpholine (89.5 mg, 0.88 mmol) and the resultant mixture was stirred at room temperature for 40 min. Then (1-ethylpyrrolidin-2-yl)methanamine (0.33 mmol, 1.1 eq.) was added to the flask and the reaction mixture was stirred for an additional 30 min, LC-MS showed the reaction was complete. The reaction was quenched with water, separated, and the aqueous layer was extracted with dichloromethane (twice). The combined organic layers were washed with 2% sodium hydroxide aqueous solution (twice) and brine (3 times), dried over anhydrous magnesium sulfate. Removal of the solvent in vacuo gave 160 mg of methyl 2-(3-((1-ethylpyrrolidin-2-yl)methylcarbamoyl)phenyl)-3,3-dimethyl-1,2,3,4-tetrahydroquinoline-6-carboxylate as a yellow oil, which was purified by column chromatography (dichloromethane: methanol=8:1) to afford 45 mg desired product as a yellow powder, yield: 34.0%.

Workup

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

Sources & evidence

ORD record
ord-008813ca51dc4d4e9066e0c19a928242
Source dataset
uspto-grants-2013_01
Patent number
US08344137B2

Reaction notes

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