Diisopropylethylamine → 4-[(R)-3-Fluoro-2-({7-methyl-4-[2-(4-tert-Butoxycarbonyl-piperazin-1-yl)-2-oxo-ethoxy]-quinoline-2-carbonyl}-amino)-propionyl]-piperazine-1-carboxylic acid butyl ester

HRID 1185592Notes

Reaction equation

HRID 1185592 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14](=[O:31])[CH2:15][O:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([CH3:27])=[CH:24][CH:25]=3)[N:20]=[C:19]([C:28](O)=[O:29])[CH:18]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH2:65]([O:69][C:70]([N:72]1[CH2:77][CH2:76][N:75]([C:78](=[O:83])[C@@H:79]([NH2:82])[CH2:80][F:81])[CH2:74][CH2:73]1)=[O:71])[CH2:66][CH2:67][CH3:68]>CN(C=O)C>[CH2:65]([O:69][C:70]([N:72]1[CH2:73][CH2:74][N:75]([C:78](=[O:83])[C@@H:79]([NH:82][C:28]([C:19]2[CH:18]=[C:17]([O:16][CH2:15][C:14]([N:11]3[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9][CH2:10]3)=[O:31])[C:26]3[C:21](=[CH:22][C:23]([CH3:27])=[CH:24][CH:25]=3)[N:20]=2)=[O:29])[CH2:80][F:81])[CH2:76][CH2:77]1)=[O:71])[CH2:66][CH2:67][CH3:68]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 685981694-((R)-2-Amino-3-fluoro-propionyl)piperazine-1-carboxylic acid butyl esterHCID 686004644-[2-(4-tert-Butoxycarbonyl-piperazin-1-yl)-2-oxo-ethoxy]-7-methyl-quinoline-2-carboxylic acid

Product 1

HCID 685984114-[(R)-3-Fluoro-2-({7-methyl-4-[2-(4-tert-Butoxycarbonyl-piperazin-1-yl)-2-oxo-ethoxy]-quinoline-2-carbonyl}-amino)-propionyl]-piperazine-1-carboxylic acid butyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 452 mg 4-[2-(4-tert-Butoxycarbonyl-piperazin-1-yl)-2-oxo-ethoxy]-7-methyl-quinoline-2-carboxylic acid in 15 ml DMF were added 0.54 ml DIPEA and 400 mg HATU. After 5 minutes 410 mg 4-((R)-2-Amino-3-fluoro-propionyl)-piperazine-1-carboxylic acid butyl ester hydrotrifluoroacetate were added and the mixture stirred for 24 h. The mixture was concentrated, diluted with DCM and washed with aqueous LiCl (4%), saturated aqueous NaHCO3 and 0.1 M HCl. The crude product thus obtained after evaporation of the solvent was used in the next step without further purification. Yield: 1.28 g.

Workup

  1. concentrationThe mixture was concentrated
  2. additiondiluted with DCM
  3. washwashed with aqueous LiCl (4%), saturated aqueous NaHCO3 and 0.1 M HCl

Sources & evidence

ORD record
ord-ad7bc8c4888f41c98340f6b7d8a5a491
Source dataset
uspto-grants-2014_03
Patent number
US08669266B2

Reaction notes

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