Diisopropylethylamine → 4-[(S)-4-Benzyloxy-2-({4-[(R)-2-((S)-2-cyclobutylcarbamoyl-pyrrolidin-1-yl)-1-methyl-2-oxo-ethoxy]-7-methyl-quinoline-2-carbonyl}-amino)-butyryl]-piperazine-1-carboxylic acid butyl ester

HRID 1185518Notes

Reaction equation

HRID 1185518 reaction equation
[CH:1]1([NH:5][C:6]([C@@H:8]2[CH2:12][CH2:11][CH2:10][N:9]2[C:13](=[O:31])[C@@H:14]([CH3:30])[O:15][C:16]2[C:25]3[C:20](=[CH:21][C:22]([CH3:26])=[CH:23][CH:24]=3)[N:19]=[C:18]([C:27](O)=[O:28])[CH:17]=2)=[O:7])[CH2:4][CH2:3][CH2:2]1.CCN(C(C)C)C(C)C.C1C=NC2N(O)N=NC=2C=1.[CH2:51]([O:55][C:56]([N:58]1[CH2:63][CH2:62][N:61]([C:64](=[O:77])[C@@H:65]([NH2:76])[CH2:66][CH2:67][O:68][CH2:69][C:70]2[CH:75]=[CH:74][CH:73]=[CH:72][CH:71]=2)[CH2:60][CH2:59]1)=[O:57])[CH2:52][CH2:53][CH3:54]>CN(C=O)C.C(Cl)CCl>[CH2:51]([O:55][C:56]([N:58]1[CH2:59][CH2:60][N:61]([C:64](=[O:77])[C@@H:65]([NH:76][C:27]([C:18]2[CH:17]=[C:16]([O:15][C@H:14]([CH3:30])[C:13]([N:9]3[CH2:10][CH2:11][CH2:12][C@H:8]3[C:6](=[O:7])[NH:5][CH:1]3[CH2:4][CH2:3][CH2:2]3)=[O:31])[C:25]3[C:20](=[CH:21][C:22]([CH3:26])=[CH:23][CH:24]=3)[N:19]=2)=[O:28])[CH2:66][CH2:67][O:68][CH2:69][C:70]2[CH:71]=[CH:72][CH:73]=[CH:74][CH:75]=2)[CH2:62][CH2:63]1)=[O:57])[CH2:52][CH2:53][CH3:54]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 685992004-((S)-2-Amino-4-benzyloxy-butyryl)-piperazine-1-carboxylic acid butyl esterHCID 686006134-[(R)-2-((S)-2-Cyclobutylcarbamoyl-pyrrolidin-1-yl)-1-methyl-2-oxo-ethoxy]-7-methyl-quinoline-2-carboxylic acid

Product 1

HCID 685984164-[(S)-4-Benzyloxy-2-({4-[(R)-2-((S)-2-cyclobutylcarbamoyl-pyrrolidin-1-yl)-1-methyl-2-oxo-ethoxy]-7-methyl-quinoline-2-carbonyl}-amino)-butyryl]-piperazine-1-carboxylic acid butyl ester

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 1.0 g 4-[(R)-2-((S)-2-Cyclobutylcarbamoyl-pyrrolidin-1-yl)-1-methyl-2-oxo-ethoxy]-7-methyl-quinoline-2-carboxylic acid in 30 ml DMF were added 1.2 g DIPEA, 319 mg HOAt and 450 mg EDC. After 5 minutes 1.1 g 4-((S)-2-Amino-4-benzyloxy-butyryl)-piperazine-1-carboxylic acid butyl ester hydrotrifluoroacetate were added and the mixture stirred for 16 h. The mixture was concentrated, diluted with DCM and washed with aqueous LiCl (4%), saturated aqueous NaHCO3 and brine. The crude product was used in the next reaction step. Yield: 2.8 g.

Workup

  1. concentrationThe mixture was concentrated
  2. additiondiluted with DCM
  3. washwashed with aqueous LiCl (4%), saturated aqueous NaHCO3 and brine
  4. customThe crude product was used in the next reaction step

Sources & evidence

ORD record
ord-723242761f0742839f7e635f9898d5a2
Source dataset
uspto-grants-2014_03
Patent number
US08669266B2

Reaction notes

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