1,2-Dichloroethane → 4-[(S)-4-tert-Butoxycarbonyl-2-({4-[2-((S)-2-cyclopropylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-7-methyl-quinoline-2-carbonyl}-amino)-butyryl]-piperazine-1-carboxylic acid ethyl ester

HRID 1185427Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1185427
[CH2:1]([O:3][C:4]([N:6]1[CH2:11][CH2:10][N:9]([C:12](=[O:42])[C@@H:13]([NH:23][C:24]([C:26]2[CH:35]=[C:34]([O:36][CH2:37][C:38](O)=[O:39])[C:33]3[C:28](=[CH:29][C:30]([CH3:41])=[CH:31][CH:32]=3)[N:27]=2)=[O:25])[CH2:14][CH2:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:8][CH2:7]1)=[O:5])[CH3:2].C(Cl)CCl.FC1C(O)=C(F)C(F)=C(F)C=1F.Cl.[CH:60]1([NH:63][C:64]([C@@H:66]2[CH2:70][CH2:69][CH2:68][NH:67]2)=[O:65])[CH2:62][CH2:61]1>CN(C=O)C.O>[CH2:1]([O:3][C:4]([N:6]1[CH2:7][CH2:8][N:9]([C:12](=[O:42])[C@@H:13]([NH:23][C:24]([C:26]2[CH:35]=[C:34]([O:36][CH2:37][C:38]([N:67]3[CH2:68][CH2:69][CH2:70][C@H:66]3[C:64](=[O:65])[NH:63][CH:60]3[CH2:61][CH2:62]3)=[O:39])[C:33]3[C:28](=[CH:29][C:30]([CH3:41])=[CH:31][CH:32]=3)[N:27]=2)=[O:25])[CH2:14][CH2:15][C:16]([O:18][C:19]([CH3:20])([CH3:22])[CH3:21])=[O:17])[CH2:10][CH2:11]1)=[O:5])[CH3:2]

Komponenten

7

Edukt 4

HCID 111,2-DichloroethaneHCID 13041PentafluorophenolHCID 66855012(S)-N-cyclopropylpyrrolidine-2-carboxamide hydrochlorideHCID 685997964-{(S)-4-tert-Butoxycarbonyl-2-[(4-carboxymethoxy-7-methyl-quinoline-2-carbonyl)-amino]-butyryl}-piperazine-1-carboxylic acid ethyl ester

Produkt 1

HCID 685984364-[(S)-4-tert-Butoxycarbonyl-2-({4-[2-((S)-2-cyclopropylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-7-methyl-quinoline-2-carbonyl}-amino)-butyryl]-piperazine-1-carboxylic acid ethyl ester

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel2×

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

To a solution of 1 g of 4-{(S)-4-tert-Butoxycarbonyl-2-[(4-carboxymethoxy-7-methyl-quinoline-2-carbonyl)-amino]-butyryl}-piperazine-1-carboxylic acid ethyl ester in 12 ml of DMF, 392 mg of EDC, 376 mg of pentafluorophenol and 392 mg of NEM was added and the reaction mixture was warmed to 50° C. for 2 h. Then, after cooling to RT, 334 mg of (S)-Pyrrolidine-2-carboxylic acid cyclopropylamide hydrochloride and 201 mg of NEM in 5 ml of DMF was added. After 1 h the reaction mixture was diluted with water and extracted with DCM (3×50 ml). The combined organic phases were dried over MgSO4 and the solvents were removed under reduced pressure. The crude product was pure enough for the next reaction step. Yield: 1.2 g.

Aufarbeitung

  1. temperatureThen, after cooling to RT
  2. extractionextracted with DCM (3×50 ml)
  3. dry with materialThe combined organic phases were dried over MgSO4
  4. customthe solvents were removed under reduced pressure
  5. customThe crude product was pure enough for the next reaction step

Quellen und Nachweise

ORD-Eintrag
ord-8b666eb0881b4c038774b4bddccbe524
Quelldatensatz
uspto-grants-2014_03
Patentnummer
US08669266B2

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