Diisopropylethylamine → ((1R)-2-(1,1'-Biphenyl-4-yl)-1-(methyl-((1R)-1-(methylcarbamoyl)-2-phenylethyl)carbamoyl)ethyl)methyl-carbamic acid tert-butylester

HRID 1601960Notes

Reaction equation

HRID 1601960 reaction equation
[C:1]1([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:6]=[CH:5][C:4]([CH2:7][C@@H:8]([N:12]([C:14]([O:16]C(C)(C)C)=[O:15])[CH3:13])[C:9]([OH:11])=O)=[CH:3][CH:2]=1.ON1C2N=C[CH:35]=[CH:36][C:31]=2N=N1.Cl.[CH3:38]N(C)CCCN=C=NCC.[CH3:49][NH:50][C:51](=[O:62])[CH:52]([NH:60][CH3:61])[CH2:53][C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1.C(N(C(C)C)CC)(C)C>C(Cl)Cl>[C:36]([O:16][C:14](=[O:15])[N:12]([C@@H:8]([C:9](=[O:11])[N:60]([CH3:61])[C@@H:52]([C:51](=[O:62])[NH:50][CH3:49])[CH2:53][C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1)[CH2:7][C:4]1[CH:3]=[CH:2][C:1]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[CH:6][CH:5]=1)[CH3:13])([CH3:35])([CH3:31])[CH3:38]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 20694694N-Boc-N-methyl-3-(biphenyl-4-yl)-D-alanineHCID 22326993N-Methyl-2-methylamino-3-phenylpropionamide

Product 1

HCID 10530245((1R)-2-(1,1'-Biphenyl-4-yl)-1-(methyl-((1R)-1-(methylcarbamoyl)-2-phenylethyl)carbamoyl)ethyl)methyl-carbamic acid tert-butylesterYield 45.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

(2R)-3-(1,1'-Biphenyl-4-yl)-2-(N-tert-butoxycarbonyl-N-methylamino)propionic acid (1.50 g; 4.23 mmol) was dissolved in methylene chloride (20 mL). 1-Hydroxy-7-azabenzotriazole (0.57 g; 4.23 mmol) and N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (0.89 g; 4.65 mmol) were added and the reaction mixture was stirred for 15 min at room temperature. N-Methyl-2-methylamino-3-phenylpropionamide (0.81 g; 4.23 mmol) and diisopropylethylamine (0.73 mL; 4.23 mmol) were added and the reaction mixture was stirred for 12 hours at room temperature. Methylene chloride (50 mL) was added and the reaction mixture was washed with water (50 mL), an aqueous solution of sodium hydrogen carbonate (sat; 50 mL), an aqueous solution of sodium hydrogen sulfate (10%; 50 mL) and water (50 mL) and dried (magnesium sulfate). The solvent was removed in vacuo and the residue was chromatographed on silica (4×25 cm) using ethyl acetate/heptane (2:1) as eluent to afford 1.02 g of ((1R)-2-(1,1'-biphenyl-4-yl)-1-(methyl-((1R)-1-methylcarbamoyl-2-phenylethyl)carbamoyl)ethyl)methylcarbamic acid tert-butyl ester.

Workup

  1. stirringthe reaction mixture was stirred for 12 hours at room temperature
  2. washthe reaction mixture was washed with water (50 mL)
  3. dry with materialan aqueous solution of sodium hydrogen carbonate (sat; 50 mL), an aqueous solution of sodium hydrogen sulfate (10%; 50 mL) and water (50 mL) and dried (magnesium sulfate)
  4. customThe solvent was removed in vacuo
  5. customthe residue was chromatographed on silica (4×25 cm)

Sources & evidence

ORD record
ord-4d9cccbd6b2a4bce86d0e9f9bb62a10f
Source dataset
uspto-grants-1999_11
Patent number
US05977178

Reaction notes

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