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 1185427Notes

Reaction equation

HRID 1185427 reaction equation
[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]

Participants

7

Reactant 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

Product 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

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
50 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-8b666eb0881b4c038774b4bddccbe524
Source dataset
uspto-grants-2014_03
Patent number
US08669266B2

Reaction notes

Loading…