Triethylamine → HCID 11432505, compound

HRID 1725661Notes

Reaction equation

HRID 1725661 reaction equation
C(N(CC)CC)C.[NH2:8][C@@H:9]1[CH2:15][CH2:14][C@@H:13]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[C:17]=2[F:23])[CH2:12][N:11]([CH2:24][C:25]([F:28])([F:27])[F:26])[C:10]1=[O:29].Cl[C:31](OC1C=CC([N+]([O-])=O)=CC=1)=[O:32].[NH:43]1[CH2:48][CH2:47][CH:46]([C:49]2[C:50](=[O:55])[NH:51][N:52]=[CH:53][CH:54]=2)[CH2:45][CH2:44]1>O1CCCC1>[F:23][C:17]1[C:18]([F:22])=[CH:19][CH:20]=[CH:21][C:16]=1[C@H:13]1[CH2:12][N:11]([CH2:24][C:25]([F:28])([F:26])[F:27])[C:10](=[O:29])[C@H:9]([NH:8][C:31]([N:43]2[CH2:44][CH2:45][CH:46]([C:49]3[C:50](=[O:55])[NH:51][N:52]=[CH:53][CH:54]=3)[CH2:47][CH2:48]2)=[O:32])[CH2:15][CH2:14]1

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 821294-Nitrophenyl chloroformateHCID 23653826(3R,6S)-3-Amino-6-(2,3-difluorophenyl)-1-(2,2,2-trifluoroethyl)azepan-2-oneHCID 57562526HCID 57562526, compound

Product 1

HCID 11432505HCID 11432505, compoundYield 54.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Triethylamine (11.5 mg, 0.104 mmol) was added to a solution (3R,6S)-3-amino-6-(2,3-difluorophenyl)-1-(2,2,2-trifluoroethyl)azepan-2-one (32 mg, 0.104 mmol) and p-nitrophenyl chloroformate (20 mg, 0.104 mmol) in tetrahydrofuran (1 mL) at 0° C. After 0.5 h, triethylamine (42 mg, 10.416 mmol) and 4-piperidin-4-ylpyridazin-3(2H)-one (19 mg, 0.104 mmol) were added and the mixture was allowed to warm to ambient temperature. After 1 h, the mixture was quenched with water, extracted with ethyl acetate, and washed with 1 N NaOH solution. The combined organic layer was dried over sodium sulfate, filtered, and concentrated. Purification by silica gel chromatography (1% methanol/dichloromethane→10% methanol/dichloromethane) gave the title compound (30 mg). MS 528.1999 (M+1).

Workup

  1. waitAfter 1 h
  2. customthe mixture was quenched with water
  3. extractionextracted with ethyl acetate
  4. washwashed with 1 N NaOH solution
  5. dry with materialThe combined organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by silica gel chromatography (1% methanol/dichloromethane→10% methanol/dichloromethane)

Sources & evidence

ORD record
ord-44f60fccc12c487ab00aafddaba687df
Source dataset
uspto-grants-2009_02
Patent number
US07491713B2

Reaction notes

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