Triethylamine → (3R*,4R*)-3-({Cyclopropyl-[2-(3-nitro-phenyl)-acetyl]-amino}-methyl)-4-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1158361Notes

Reaction equation

HRID 1158361 reaction equation
CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[N+:25]([C:28]1[CH:29]=[C:30]([CH2:34][C:35]([OH:37])=O)[CH:31]=[CH:32][CH:33]=1)([O-:27])=[O:26].[C:38]([O:42][C:43]([N:45]1[CH2:49][C@@H:48]([CH2:50][N:51]([CH:68]([CH3:70])[CH3:69])[C:52](=[O:67])[C:53]2[CH:58]=[CH:57][C:56]([O:59][CH3:60])=[C:55]([O:61][CH2:62][CH2:63][CH2:64][O:65][CH3:66])[CH:54]=2)[C@H:47]([CH2:71][NH:72][CH:73]2[CH2:75][CH2:74]2)[CH2:46]1)=[O:44])([CH3:41])([CH3:40])[CH3:39].C(N(CC)CC)C.C([O-])(O)=O.[Na+]>CC#N>[C:38]([O:42][C:43]([N:45]1[CH2:49][C@@H:48]([CH2:50][N:51]([CH:68]([CH3:69])[CH3:70])[C:52](=[O:67])[C:53]2[CH:58]=[CH:57][C:56]([O:59][CH3:60])=[C:55]([O:61][CH2:62][CH2:63][CH2:64][O:65][CH3:66])[CH:54]=2)[C@H:47]([CH2:71][N:72]([CH:73]2[CH2:74][CH2:75]2)[C:35](=[O:37])[CH2:34][C:30]2[CH:31]=[CH:32][CH:33]=[C:28]([N+:25]([O-:27])=[O:26])[CH:29]=2)[CH2:46]1)=[O:44])([CH3:40])([CH3:41])[CH3:39]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 158763-Nitrophenylacetic acidHCID 516892Sodium BicarbonateHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68616408(3R*,4R*)-3-Cyclopropylaminomethyl-4-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 68618278(3R*,4R*)-3-({Cyclopropyl-[2-(3-nitro-phenyl)-acetyl]-amino}-methyl)-4-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

At 0° C. HBTU (426 mg, 1.12 mmol) is added to a solution of 3-nitrophenylacetic acid (187 mg, 1.03 mmol) in CH3CN (10 mL) and the resulting solution is stirred for 10 min. Then a solution of (3R*,4R*)-3-cyclopropylaminomethyl-4-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (0.2 g, 0.375 mmol). (500 mg, 0.94 mmol) and triethylamine (1.04 mL, 7.5 mmol) in CH3CN (10 mL) is added at 0° C. and the reaction mixture is stirred at RT for another 2 h. For workup a sat. solution of NaHCO3 is added and the mixture is extracted with ethyl acetate. Washing of the combined extracts with brine, drying (Na2SO4), filtration and evaporation of the solvent affords the crude product which is purified by flash chromatography on silica gel (eluent: CH2Cl2 to CH2Cl2/MeOH 9:1) to give the title compound. MS (LC-MS): 597.0 [M+H-Boc]+; tR (HPLC, Macherey-Nagel Nucleosil C18 column, 10-100% CH3CN/H2O/5 min, 100% CH3CN/3 min, CH3CN and H2O containing 0.1% TFA, flow: 1.5 mumin): 6.47 min.

Workup

  1. customAt 0° C
  2. stirringthe reaction mixture is stirred at RT for another 2 h
  3. extractionthe mixture is extracted with ethyl acetate
  4. washWashing of the combined extracts with brine
  5. customdrying
  6. filtration(Na2SO4), filtration and evaporation of the solvent
  7. customaffords the crude product which
  8. customis purified by flash chromatography on silica gel (eluent: CH2Cl2 to CH2Cl2/MeOH 9:1)

Sources & evidence

ORD record
ord-a925cdd059e0493ca4e04e3ee1862e1c
Source dataset
uspto-grants-2010_10
Patent number
US07807709B2

Reaction notes

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