1,2-Dichloroethane → {(S)-6-Oxo-7-[2-(2,2,3,3,3-pentafluoro-propylcarbamoyl)-propionylamino]-6,7-dihydro-dibenzo[b,d]azepin-5-yl}-acetic acid methyl ester

HRID 30994Notes

Reaction equation

HRID 30994 reaction equation
[CH3:1][O:2][C:3](=[O:22])[CH2:4][N:5]1[C:11](=[O:12])[C@@H:10]([NH2:13])[C:9]2[CH:14]=[CH:15][CH:16]=[CH:17][C:8]=2[C:7]2[CH:18]=[CH:19][CH:20]=[CH:21][C:6]1=2.[CH3:23][CH:24]([C:28]([NH:30][CH2:31][C:32]([F:38])([F:37])[C:33]([F:36])([F:35])[F:34])=[O:29])[C:25](O)=[O:26].ON1C2C=CC=CC=2N=N1.C(N(C(C)C)C(C)C)C.C(Cl)CCl>C1COCC1>[CH3:1][O:2][C:3](=[O:22])[CH2:4][N:5]1[C:11](=[O:12])[C@@H:10]([NH:13][C:25](=[O:26])[CH:24]([C:28](=[O:29])[NH:30][CH2:31][C:32]([F:37])([F:38])[C:33]([F:34])([F:36])[F:35])[CH3:23])[C:9]2[CH:14]=[CH:15][CH:16]=[CH:17][C:8]=2[C:7]2[CH:18]=[CH:19][CH:20]=[CH:21][C:6]1=2

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 210724942-Methyl-N-(2,2,3,3,3-pentafluoro-propyl)-malonamic acidHCID 58972470HCID 58972470, compound

Product 1

HCID 58972529{(S)-6-Oxo-7-[2-(2,2,3,3,3-pentafluoro-propylcarbamoyl)-propionylamino]-6,7-dihydro-dibenzo[b,d]azepin-5-yl}-acetic acid methyl esterYield 70%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

((S)-7-Amino-6-oxo-6,7-dihydro-dibenzo[b,d]azepin-5-yl)-acetic acid methyl ester (25 mg, 0.85 mmol) were dissolved in THF and subsequently treated with 2-methyl-N-(2,2,3,3,3-pentafluoro-propyl)-malonamic acid (25 mg, 0.1 mmol), 1-hydroxybenzotriazole (11.6 mg, 0.85 mmol), N-ethyldiisopropylamine (0.03 ml, 0.17 mmol) and EDC (16.5 mg, 0.85 mmol). After stirring for 2.5 h at ambient temperature, the reaction mixture is quenched with water and extracted with ethyl acetate. The aqueous phase is extracted twice with ethyl acetate and the combined organic layers are extracted with water (2×5 ml) and saturated aqueous sodium chloride (5 ml), combined, dried over anhydrous sodium sulfate and evaporated to dryness. Chromatography (silica, eluent cyclohexane/ethyl acetate 65/35) afforded the product as colorless solid (70%). MS: m/e=528 (M+H+).

Workup

  1. customthe reaction mixture is quenched with water
  2. extractionextracted with ethyl acetate
  3. extractionThe aqueous phase is extracted twice with ethyl acetate
  4. extractionthe combined organic layers are extracted with water (2×5 ml) and saturated aqueous sodium chloride (5 ml)
  5. dry with materialdried over anhydrous sodium sulfate
  6. customevaporated to dryness

Sources & evidence

ORD record
ord-3a579f662dd540eb8ed3cb244c79d21b
Source dataset
uspto-grants-2008_09
Patent number
US07425551B2

Reaction notes

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