Diisopropylethylamine → (R)-4-{(S)-4-Carboxy-2-[(5-{2-[(S)-2-(Cyclopropylmethyl carbamoyl)-pyrrolidin-1-yl]-2-oxo-ethoxy}-1-phenyl-1H-pyrazole-3-carbonyl)-amino]-butyryl}-2-methyl-piperazine-1-carboxylic acid ethyl ester

HRID 1970536Notes

Reaction equation

HRID 1970536 reaction equation
C([O:5][C:6](=[O:43])[CH2:7][CH2:8][C@H:9]([NH:13][C:14]([C:16]1[CH:20]=[C:19]([O:21][CH2:22][C:23]([N:25]2[CH2:29][CH2:28][CH2:27][C@H:26]2[C:30](=[O:36])[NH:31][CH2:32][CH:33]2[CH2:35][CH2:34]2)=[O:24])[N:18]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[N:17]=1)=[O:15])[C:10](O)=[O:11])(C)(C)C.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.[CH2:77]([O:79][C:80]([N:82]1[CH2:87][CH2:86][NH:85][CH2:84][C@H:83]1[CH3:88])=[O:81])[CH3:78]>CN(C=O)C>[CH2:77]([O:79][C:80]([N:82]1[CH2:87][CH2:86][N:85]([C:10](=[O:11])[C@@H:9]([NH:13][C:14]([C:16]2[CH:20]=[C:19]([O:21][CH2:22][C:23]([N:25]3[CH2:29][CH2:28][CH2:27][C@H:26]3[C:30](=[O:36])[NH:31][CH2:32][CH:33]3[CH2:35][CH2:34]3)=[O:24])[N:18]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[N:17]=2)=[O:15])[CH2:8][CH2:7][C:6]([OH:43])=[O:5])[CH2:84][C@H:83]1[CH3:88])=[O:81])[CH3:78]

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 45099581(R)-2-Methyl-piperazine-1-carboxylic acid ethyl esterHCID 66855222(S)-2-({5-[2-((S)-2-(Cyclopropylmethyl-carbamoyl)-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-pentanedioic acid 5-tert-butyl ester

Product 1

HCID 66854473(R)-4-{(S)-4-Carboxy-2-[(5-{2-[(S)-2-(Cyclopropylmethyl carbamoyl)-pyrrolidin-1-yl]-2-oxo-ethoxy}-1-phenyl-1H-pyrazole-3-carbonyl)-amino]-butyryl}-2-methyl-piperazine-1-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 100 mg (S)-2-({5-[2-((S)-2-(Cyclopropylmethyl-carbamoyl)-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-pentanedioic acid 5-tert-butyl ester in 6 ml DMF were added 28 μl DIPEA, 64 mg HATU and 29 mg (R)-2-Methyl-piperazine-1-carboxylic acid ethyl ester. After stirring for 16 h the solution was concentrated, the residue dissolved in 1.5 ml dichloromethane and treated with 560 μl TFA. After stirring for 16 h the solvents were removed under reduced pressure and the residue purified by preparative HPLC (C18 reverse phase column, elution with a water/MeCN gradient with 0.1% TFA). The fractions containing the product were lyophilized to yield the pure product. Yield: 65 mg MS (ES+): m/e=696.

Workup

  1. concentrationwas concentrated
  2. dissolutionthe residue dissolved in 1.5 ml dichloromethane
  3. additiontreated with 560 μl TFA
  4. stirringAfter stirring for 16 h the solvents
  5. customwere removed under reduced pressure
  6. customthe residue purified by preparative HPLC (
  7. washC18 reverse phase column, elution with a water/MeCN gradient with 0.1% TFA)
  8. additionThe fractions containing the product
  9. customto yield the pure product

Sources & evidence

ORD record
ord-07fe2bacc52443aab0073fba5d51bb9e
Source dataset
uspto-grants-2013_04
Patent number
US08426420B2

Reaction notes

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