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

HRID 1185437Notes

Reaction equation

HRID 1185437 reaction equation
[CH2:1]([O:3][C:4]([N:6]1[CH2:11][CH2:10][N:9]([C:12](=[O:41])[C@@H:13]([NH:23][C:24]([C:26]2[CH:35]=[C:34]([O:36][CH2:37][C:38]([OH:40])=O)[C:33]3[C:28](=[CH:29][CH:30]=[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:59]1([NH:62][C:63]([C@@H:65]2[CH2:69][CH2:68][CH2:67][NH:66]2)=[O:64])[CH2:61][CH2:60]1>CN(C=O)C.O>[CH2:1]([O:3][C:4]([N:6]1[CH2:7][CH2:8][N:9]([C:12](=[O:41])[C@@H:13]([NH:23][C:24]([C:26]2[CH:35]=[C:34]([O:36][CH2:37][C:38]([N:66]3[CH2:67][CH2:68][CH2:69][C@H:65]3[C:63](=[O:64])[NH:62][CH:59]3[CH2:60][CH2:61]3)=[O:40])[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[N:27]=2)=[O:25])[CH2:14][CH2:15][C:16]([O:18][C:19]([CH3:21])([CH3:22])[CH3:20])=[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 686002284-{(S)-4-tert-Butoxycarbonyl-2-[(4-carboxymethoxy-quinoline-2-carbonyl)-amino]-butyryl}-piperazine-1-carboxylic acid ethyl ester

Product 1

HCID 685985494-[(S)-4-tert-Butoxycarbonyl-2-({4-[2-((S)-2-cyclopropylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-quinoline-2-carbonyl}-amino)-butyryl]-piperazine-1-carboxylic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 2.2 g of 4-{(S)-4-tert-Butoxycarbonyl-2-[(4-carboxymethoxy-quinoline-2-carbonyl)-amino]-butyryl}-piperazine-1-carboxylic acid ethyl ester in 30 ml of DMF, 883 mg of EDC, 848 mg of pentafluorophenol and 885 mg of NEM was added and the reaction mixture was stirred for 2 h at RT. Then, 732 mg of (S)-Pyrrolidine-2-carboxylic acid cyclopropylamide hydrochloride and 442 mg of NEM in 5 ml of DMF was added. After 2 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: 2.9 g.

Workup

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

Sources & evidence

ORD record
ord-58530d520b0c442786bcc9354609cde0
Source dataset
uspto-grants-2014_03
Patent number
US08669266B2

Reaction notes

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