Triethylamine → HCID 68617790, compound

HRID 1158375Notes

Reaction equation

HRID 1158375 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][NH2:35])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:36][C:37]([C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)([CH3:41])[C:38](O)=[O:39].CCN(CC)CC.ON1C2N=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:9][C@@H:10]([CH2:34][NH:35][C:38](=[O:39])[C:37]([CH3:36])([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[CH3:41])[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)[CH2:12]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 132222-Phenylisobutyric acidHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 68617423HCID 68617423, compound

Product 1

HCID 68617790HCID 68617790, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (3R,4R)-3-aminomethyl-4-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (200 mg, 0.405 mmol) and α,α-dimethylphenylacetic acid (101 mg, 0.608 mmol) in CH2Cl2 (3 mL) is subsequently added Et3N (0.085 mL, 0.608 mmol), 1-hydroxy-7-azabenzotriazole (84 mg, 0.608 mmol; commercially available from ABCR, AV24631) and N-(3-dimethylaminopropyl)-N′-ethyl-carbodiimide HCl (118 mg, 0.608 mmol). Stirring is continued overnight at room temperature, the mixture is then diluted with CH2Cl2, and the organic layer is subsequently washed with 2N HCl, saturated aqueous NaHCO3 and brine, dried (MgSO4) and concentrated. Purification by RP-HPLC on a PrepC18 OBD column (dimensions: 30×100 mm; 5 μM particle size, SunFire Ltd) and using a 95-5% gradient of MeCN/H2O 5:95 (containing 0.1% TFA) to MeCN/H2O 95:5 (containing 0.1% TFA) over 20 min gives the title compound as colorless oil. MS [M]+=640.2. tR (HPLC, Nucleosil C18HD column, 20-100% CH3CN/H2O/6 min, 100% CH3CN/2 min, CH3CN and H2O containing 0.1% TFA, flow: 1 mL/min): 5.2 min.

Workup

  1. washthe organic layer is subsequently washed with 2N HCl, saturated aqueous NaHCO3 and brine
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated
  4. customPurification by RP-HPLC on a PrepC18 OBD column (dimensions: 30×100 mm; 5 μM particle size, SunFire Ltd)
  5. customover 20 min

Sources & evidence

ORD record
ord-fd2414d93ec247af94d3fae6ac14c89f
Source dataset
uspto-grants-2010_10
Patent number
US07807709B2

Reaction notes

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