Phenylacetic Acid → (3R,4R)-3-[(Cyclopropyl-phenylacetyl-amino)-methyl]-4-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1158358Notes

Reaction equation

HRID 1158358 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([CH2:13][N:14]([CH:31]([CH3:33])[CH3:32])[C:15](=[O:30])[C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[C:18]([O:24][CH2:25][CH2:26][CH2:27][O:28][CH3:29])[CH:17]=2)[C@H:10]([CH2:34][NH:35][CH:36]2[CH2:38][CH2:37]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN(CC)CC.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[C:69]1([CH2:75][C:76](O)=[O:77])[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=1>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([CH2:13][N:14]([CH:31]([CH3:32])[CH3:33])[C:15](=[O:30])[C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[C:18]([O:24][CH2:25][CH2:26][CH2:27][O:28][CH3:29])[CH:17]=2)[C@H:10]([CH2:34][N:35]([CH:36]2[CH2:37][CH2:38]2)[C:76](=[O:77])[CH2:75][C:69]2[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=2)[CH2:9]1)=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

7

Reactant 5

HCID 999Phenylacetic AcidHCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 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 68618183(3R,4R)-3-[(Cyclopropyl-phenylacetyl-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 6344DichloromethaneSolvent2×

Procedure

To 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 (0.30 g, 0.56 mmol) in CH2Cl2 (6 mL) are subsequently added Et3N (0.094 mL, 0.67 mmol), 1-hydroxy-benzotriazol hydrate (0.09 g, 0.67 mmol), N-(3-dimethylaminopropyl)-N′-ethyl-carbodiimide hydrochloride (0.129 g, 0.67 mmol) and phenylacetic acid (0.09 g, 0.67 mmol), followed by stirring overnight. The reaction mixture is diluted with CH2Cl2 and then washed with 1N HCl (5 mL), saturated aqueous NaHCO3 and brine, the organic layer is dried over MgSO4 and concentrated. Purification by flash chromatography (eluent: hexane/AcOEt 25:75, then AcOEt 100%) gives the title compound as colorless oil. MS (LC-MS): 652.4 [M+H]+. tR (HPLC, Nucleosil C18HD column, 5-100% CH3CN/H2O/6 min, 100% CH3CN/1.5 min, CH3CN and H2O containing 0.1% TFA, flow: 1 mL/min): 5.80 min.

Workup

  1. washwashed with 1N HCl (5 mL), saturated aqueous NaHCO3 and brine
  2. dry with materialthe organic layer is dried over MgSO4
  3. concentrationconcentrated
  4. customPurification by flash chromatography (eluent

Sources & evidence

ORD record
ord-df85466bf2b04b2b806eccc7abf649ca
Source dataset
uspto-grants-2010_10
Patent number
US07807709B2

Reaction notes

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