1,1'-Carbonyldiimidazole → HCID 66720877, compound

HRID 1040355Notes

Reaction equation

HRID 1040355 reaction equation
C1N=CN(C(N2C=NC=C2)=O)C=1.[Cl:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[C:21]([C:29]3[C:34]([O:35][CH3:36])=[CH:33][CH:32]=[CH:31][C:30]=3[O:37][CH3:38])=[CH:22][CH:23]=[C:24]([C:26](O)=[O:27])[CH:25]=2)=[CH:16][C:15]=1[O:39][CH2:40][CH2:41][CH2:42][N:43]([CH3:45])[CH3:44].[NH2:46][CH:47]([CH:52]([CH3:54])[CH3:53])[CH2:48][C:49]([OH:51])=[O:50]>C1COCC1.CN(C=O)C>[ClH:13].[Cl:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[C:21]([C:29]3[C:30]([O:37][CH3:38])=[CH:31][CH:32]=[CH:33][C:34]=3[O:35][CH3:36])=[CH:22][CH:23]=[C:24]([C:26]([NH:46][CH:47]([CH:52]([CH3:54])[CH3:53])[CH2:48][C:49]([OH:51])=[O:50])=[O:27])[CH:25]=2)=[CH:16][C:15]=1[O:39][CH2:40][CH2:41][CH2:42][N:43]([CH3:44])[CH3:45]

Participants

6

Reactant 3

HCID 682631,1'-Carbonyldiimidazole2×HCID 193411beta-LeucineHCID 66720898HCID 66720898, compound

Product 1

HCID 66720877HCID 66720877, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
55 °C

Procedure

Add 141 mg (0.87 mmol) of CDI to a solution of 315 mg (0.67 mmol) of 4″-chloro-3″-[3-(dimethylamino)propoxy]-2,6-dimethoxy-1,1′:2′,1″-terphenyl-4′-carboxylic acid in 7 mL of anhydrous THF, and stir the reaction mixture at 55° C. for 1 h under argon. Add 70 mg (0.43 mmol) of carbonyl-1,1′-diimidazole and continue the reaction for 1 h at 50° C. Then add a suspension of 97 mg (0.74 mmol) of racemic 3-amino-4-methylpentanoic acid in a mixture of 4 mL of THF and 0.8 mL of DMF and continue stirring for 15 h at 55° C. After concentration under reduced pressure, distribute the residue obtained in 30 mL of a 2:1 DCM/water mixture. Wash the organic phase with 10 mL of water, dry over magnesium sulphate (MgSO4) and concentrate under reduced pressure. Purify the residue obtained by silica gel column chromatography, eluting with a DCM/methanol gradient from 0 to 5% of methanol. After concentration under reduced pressure, solidify the residue in ether, filter on a frit and wash with ether. We thus obtain 91 mg of 3-[({4″-chloro-3″-[3-(dimethylamino)propoxy]-2,6-dimethoxy-1,1′:2′,1″-terphenyl-4′-yl}carbonyl)amino]-4-methylpentanoic acid hydrochloride in the form of white powder.

Workup

  1. customthe reaction for 1 h at 50° C
  2. additionThen add
  3. stirringcontinue stirring for 15 h at 55° C
  4. concentrationAfter concentration under reduced pressure
  5. customobtained in 30 mL of a 2:1 DCM/water mixture
  6. washWash the organic phase with 10 mL of water
  7. dry with materialdry over magnesium sulphate (MgSO4)
  8. concentrationconcentrate under reduced pressure
  9. customPurify the residue
  10. customobtained by silica gel column chromatography
  11. washeluting with a DCM/methanol gradient from 0 to 5% of methanol
  12. concentrationAfter concentration under reduced pressure
  13. filtrationfilter on a frit
  14. washwash with ether

Sources & evidence

ORD record
ord-f4ac7c54c38f4de8b3736216d17b8f88
Source dataset
uspto-grants-2013_10
Patent number
US08552201B2

Reaction notes

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