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

HRID 1970483Notes

Reaction equation

HRID 1970483 reaction equation
[CH2:1]([O:3][C:4]([N:6]1[CH2:11][CH2:10][N:9]([C:12](=[O:49])[C@@H:13]([NH:23][C:24]([C:26]2[CH:30]=[C:29]([O:31][CH2:32][C:33]([N:35]3[CH2:39][CH2:38][CH:37]([C:40]([OH:42])=O)[CH2:36]3)=[O:34])[N:28]([C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)[N:27]=2)=[O:25])[CH2:14][CH2:15][C:16]([O:18]C(C)(C)C)=[O:17])[CH2:8][CH2:7]1)=[O:5])[CH3:2].CC[N:52]([CH:56]([CH3:58])[CH3:57])C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C1(N)CC1.C([O-])(O)=O.[Na+]>CN(C=O)C>[CH2:1]([O:3][C:4]([N:6]1[CH2:7][CH2:8][N:9]([C:12](=[O:49])[C@@H:13]([NH:23][C:24]([C:26]2[CH:30]=[C:29]([O:31][CH2:32][C:33]([N:35]3[CH2:39][CH2:38][CH:37]([C:40](=[O:42])[NH:52][CH:56]4[CH2:58][CH2:57]4)[CH2:36]3)=[O:34])[N:28]([C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)[N:27]=2)=[O:25])[CH2:14][CH2:15][C:16]([OH:18])=[O:17])[CH2:10][CH2:11]1)=[O:5])[CH3:2]

Participants

7

Reactant 5

HCID 69828CyclopropylamineHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 668547954-[(S)-4-tert-Butoxycarbonyl-2-({5-[2-(3-carboxy-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-butyryl]-piperazine-1-carboxylic acid ethyl ester

Product 1

HCID 668551414-[(S)-4-Carboxy-2-({5-[2-(3-cyclopropylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-butyryl]-piperazine-1-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 200 mg 4-[(S)-4-tert-butoxycarbonyl-2-({5-[2-(3-carboxy-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-butyryl]-piperazine-1-carboxylic acid ethyl ester in 5 ml DMF were added 48 μl DIPEA, 11 mg HATU and 20 μl cyclopropylamine. After stirring for 12 h saturated aqueous NaHCO3 solution was added and the mixture loaded on a Chem Elut® cartridge, the crude product being eluted with dichloromethane. The solution was concentrated to a volume of 5 ml and stirred in the presence of 324 μl TFA. After stirring for 14 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: 30 mg MS (ES+): m/e=668.

Workup

  1. additionwas added
  2. washthe crude product being eluted with dichloromethane
  3. concentrationThe solution was concentrated to a volume of 5 ml
  4. stirringAfter stirring for 14 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-be6b9aebdd8a43ecbc41c420ac18577d
Source dataset
uspto-grants-2013_04
Patent number
US08426420B2

Reaction notes

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