Diisopropylethylamine → HCID 44129526, compound

HRID 1970597Notes

Reaction equation

HRID 1970597 reaction equation
[F:1][C:2]1([F:8])[CH2:4][CH:3]1[C:5](O)=[O:6].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.[CH2:42]([O:44][C:45]([N:47]1[CH2:52][CH2:51][N:50]([C:53](=[O:88])[C@@H:54]([NH:58][C:59]([C:61]2[CH:65]=[C:64]([O:66][CH2:67][C:68]([N:70]3[CH2:74][CH2:73][CH2:72][C@H:71]3[C:75](=[O:81])[NH:76][CH:77]3[CH2:80][CH2:79][CH2:78]3)=[O:69])[N:63]([C:82]3[CH:87]=[CH:86][CH:85]=[CH:84][CH:83]=3)[N:62]=2)=[O:60])[CH2:55][CH2:56][NH2:57])[CH2:49][CH2:48]1)=[O:46])[CH3:43]>CN(C=O)C.ClCCl>[CH2:42]([O:44][C:45]([N:47]1[CH2:52][CH2:51][N:50]([C:53](=[O:88])[C@@H:54]([NH:58][C:59]([C:61]2[CH:65]=[C:64]([O:66][CH2:67][C:68]([N:70]3[CH2:74][CH2:73][CH2:72][C@H:71]3[C:75](=[O:81])[NH:76][CH:77]3[CH2:80][CH2:79][CH2:78]3)=[O:69])[N:63]([C:82]3[CH:87]=[CH:86][CH:85]=[CH:84][CH:83]=3)[N:62]=2)=[O:60])[CH2:55][CH2:56][NH:57][C:5]([CH:3]2[CH2:4][C:2]2([F:8])[F:1])=[O:6])[CH2:49][CH2:48]1)=[O:46])[CH3:43]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 27828232,2-Difluorocyclopropane-1-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 668549194-[(S)-4-Amino-2-({5-[2-((S)-2-cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-butyryl]-piperazine-1-carboxylic acid ethyl ester

Product 1

HCID 44129526HCID 44129526, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 19 mg 2,2-Difluorocyclopropane carboxylic acid in 3 ml DMF were added 0.03 ml DIPEA, 58 mg HATU and 100 mg 4-[(S)-4-Amino-2-({5-[2-((S)-2-cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-butyryl]-piperazine-1-carboxylic acid ethyl ester. After stirring for 12 h it was diluted with dichlormethane and extracted with aqueous LiCl (4% w/w), aqueous NaHCO3 and 0.1 M HCl. The crude product obtained after evaporation of the solvent was purified by preparative HPLC (C18 reverse phase column, elution with a water/MeCN gradient with 0.1% TFA) to give the title compound. Yield: 55 mg MS (ES+): m/e=756.

Workup

  1. extractionextracted with aqueous LiCl (4% w/w), aqueous NaHCO3 and 0.1 M HCl
  2. customThe crude product obtained
  3. customafter evaporation of the solvent
  4. customwas purified by preparative HPLC (
  5. washC18 reverse phase column, elution with a water/MeCN gradient with 0.1% TFA)

Sources & evidence

ORD record
ord-9d504de610e1432ba5058871c5c2a244
Source dataset
uspto-grants-2013_04
Patent number
US08426420B2

Reaction notes

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