1,1'-Carbonyldiimidazole → HCID 58476281, compound

HRID 1801318Notes

Reaction equation

HRID 1801318 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]([OH:20])=O)[C:9]([CH3:25])([CH3:24])[CH2:8]2)=[O:4].[C:26]([N:33]1[CH:37]=[CH:36][N:35]=[CH:34]1)([N:28]1C=CN=C1)=O.N1C=CN=CC=1N.N12CCCN=C1CCCCC2>O1CCCC1.C(OCC)(=O)C.ClCCl>[CH3:24][C:9]1([CH3:25])[CH2:8][C:7]2[C:12](=[CH:13][CH:14]=[C:5]([C:3]([O:2][CH3:1])=[O:4])[CH:6]=2)[NH:11][CH:10]1[C:15]1[CH:23]=[CH:22][CH:21]=[C:17]([C:18](=[O:20])[NH:28][C:26]2[CH:34]=[N:35][CH:36]=[CH:37][N:33]=2)[CH:16]=1

Participants

8

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 78747AminopyrazineHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 674419763-(6-(Methoxycarbonyl)-3,3-dimethyl-1,2,3,4-tetrahydroquinolin-2-yl)benzoic acid

Product 1

HCID 58476281HCID 58476281, compoundYield 47.7%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of 3-(6-(methoxycarbonyl)-3,3-dimethyl-1,2,3,4-tetrahydroquinolin-2-yl)benzoic acid (330 mg, 0.88 mmol) and 1,1′-carbonyldiimidazole (500 mg, 3.08 mmol) in tetrahydrofuran (6 mL) was heated to 60° C. for 2 h, then was cooled to room temperature and treated with pyrazin-2-amine (92.2 mg, 0.97 mmol,). After stirring for 20 min, the reaction mixture was treated with dropwise addition of a solution of 1,8-diazabicyclo[5.4.0]undec-7-ene (670 mg, 4.4 mmol) in tetrahydrofuran (2 mL). Upon completion of addition, the resultant mixture was stirred overnight. Thin layer chromatography (dichloromethane:ethyl acetate=5:1) showed the reaction was nearly complete. The reaction mixture was quenched with brine and acidified with 1N hydrochloric acid solution to pH=6, extracted with ethyl acetate (twice). The combined organic layers were washed with brine for 3 times, dried over anhydrous magnesium sulfate. Removal of the solvent in vacuo gave crude product, which was purified by column chromatography (dichloromethane:ethyl acetate=5:1) to afford 175 mg of methyl 3,3-dimethyl-2-(3-(pyrazin-2-ylcarbamoyl)-phenyl)-1,2,3,4-tetrahydroquinoline-6-carboxylate as a white solid. Yield: 47.5%. MS (ESI+APCI) M+1=417.2.

Workup

  1. additionUpon completion of addition
  2. customThe reaction mixture was quenched with brine
  3. extractionextracted with ethyl acetate (twice)
  4. washThe combined organic layers were washed with brine for 3 times
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customRemoval of the solvent in vacuo
  7. customgave crude product, which
  8. customwas purified by column chromatography (dichloromethane:ethyl acetate=5:1)

Sources & evidence

ORD record
ord-2383652971ea4313b615917f390a0196
Source dataset
uspto-grants-2013_01
Patent number
US08344137B2

Reaction notes

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