Triethylamine → HCID 51348929, compound

HRID 1507657Notes

Reaction equation

HRID 1507657 reaction equation
[Cl-].[NH2:2][C:3]1([CH2:33][CH2:34][OH:35])[CH2:7][CH2:6][C@@H:5]([C:8]([NH:10][C@H:11]([CH:30]([CH3:32])[CH3:31])[C:12]([N:14]2[CH2:19][CH2:18][C@@:17]([C:21]3[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=3)([OH:20])[C:16]([CH3:29])([CH3:28])[CH2:15]2)=[O:13])=[O:9])[CH2:4]1.[C:36](C1NC=CN=1)(C1NC=CN=1)=[O:37].C(N(CC)CC)C>C1COCC1>[Cl:27][C:24]1[CH:25]=[CH:26][C:21]([C@@:17]2([OH:20])[CH2:18][CH2:19][N:14]([C:12](=[O:13])[C@H:11]([NH:10][C:8]([C@@H:5]3[CH2:6][CH2:7][C:3]4([CH2:33][CH2:34][O:35][C:36](=[O:37])[NH:2]4)[CH2:4]3)=[O:9])[CH:30]([CH3:32])[CH3:31])[CH2:15][C:16]2([CH3:29])[CH3:28])=[CH:22][CH:23]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 5250894Bis-(1H-imidazol-2-YL)-methanoneHCID 131731995HCID 131731995, compound

Product 1

HCID 51348929HCID 51348929, compoundYield 6.33%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (1R)-3-amino-N-((R)-1-((S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl)-3-methyl-1-oxobutan-2-yl)-3-(2-hydroxyethyl)cyclopentanecarboxamide (from step F, 30 mg, 0.061 mmol) in THF (1 mL) was added carbonyl diimidazole (14.77 mg, 0.091 mmol) and triethylamine (0.021 mL, 0.152 mmol). The resulting mixture was stirred at room temperature for 4 hours. The reaction mixture was concentrated and subjected preparative HPLC(Shimadzu VP-ODS 20×100 mm, 8 min. gradient, Solvent A: 10% MeOH, 90% H2O, 0.1% TFA; Solvent B: 90% MeOH, 10% H2O, 0.1% TFA; wavelength: 220 nM) to yield the desired product as a diastereomer mixture. The diastereomer mixture was subjected to chiral preparative HPLC (Column: ChiralPak ASH, 250×3 cm, 5 μm; Flow rate: 120 mL/min; Mobile Phase: CO2/MeOH=80/20; Inj. Vol.=2.0 mL, Wavelength=220 nM; isomer 1, retention time=5.75 min; isomer 2, retention time=9.10 min) to yield the individual diasteromers (2 mg for each isomer, 3.85 μmol, 6.33% yield) as a solid.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customHPLC(Shimadzu VP-ODS 20×100 mm, 8 min. gradient, Solvent A

Sources & evidence

ORD record
ord-efdde996ad6b4def817878879b1e3484
Source dataset
uspto-grants-2015_12
Patent number
US09221819B2

Reaction notes

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