Diisopropylethylamine → ((1R)-2-(Benzo[b]thiophen-3-yl)-1-(methyl-((1R)-1-methylcarbamoyl-2-phenyl-ethyl)carbamoyl)ethyl)-methylcarbamic acid tert-butylester

HRID 1601974Notes

Reaction equation

HRID 1601974 reaction equation
[S:1]1[CH:5]=[C:4]([CH2:6][C@@H:7]([N:11]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH3:12])[C:8](O)=[O:9])[C:3]2[CH:20]=[CH:21][CH:22]=[CH:23][C:2]1=2.ON1C2N=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[CH3:46][NH:47][C:48](=[O:59])[C@H:49]([NH:57][CH3:58])[CH2:50][C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1.C(N(C(C)C)CC)(C)C>C(Cl)Cl>[C:16]([O:15][C:13](=[O:14])[N:11]([C@@H:7]([C:8](=[O:9])[N:57]([CH3:58])[C@@H:49]([C:48](=[O:59])[NH:47][CH3:46])[CH2:50][C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1)[CH2:6][C:4]1[C:3]2[CH:20]=[CH:21][CH:22]=[CH:23][C:2]=2[S:1][CH:5]=1)[CH3:12])([CH3:17])([CH3:19])[CH3:18]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10607786(R)-N-methyl-2-(methylamino)-3-phenylpropanamideHCID 54409748(2R)-3-(Benzo[b]thiophen-3-yl)-2-(tert-butoxycarbonyl-methylamino)propionic acid

Product 1

HCID 10839402((1R)-2-(Benzo[b]thiophen-3-yl)-1-(methyl-((1R)-1-methylcarbamoyl-2-phenyl-ethyl)carbamoyl)ethyl)-methylcarbamic acid tert-butylesterYield 29.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

(2R)-3-(Benzo[b]thiophen-3-yl)-2-(tert-butoxycarbonyl-methylamino)propionic acid (2.00 g; 5.96 mmol) was dissolved in methylene chloride (10 mL). 1-Hydroxy-7-azabenzotriazole (0.81 g; 5.96 mmol) and N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (1.26 g; 6.56 mmol) were added. The reaction mixture was stirred for 15 min at room temperature. (2R)-N-Methyl-2-methylamino-3-phenylpropionamide (1.15 g; 5.96 mmol) was dissolved in methylene chloride (10 mL) and added. Diisopropylethylamine (1.02 mL; 5.96 mmol) were added. The reaction mixture was stirred for 48 hours. Methylene chloride (10 mL) was added. The reaction was washed with water (30 mL), an aqueous solution of sodium hydrogen sulfate (10%; 30 mL), an aqueous solution of sodium hydrogen carbonate (saturated; 30 mL) and dried (magnesium sulfate). The solvent was removed in vacuo and the residue was chromatographed on silica (3×30 cm) using ethyl acetate/methylene chloride (1:1) as eluent to afford 0.89 g of ((1R)-2-(benzo[b]thiophen-3-yl)-1-(methyl-((1R)-1-methylcarbamoyl-2-phenylethyl)carbamoyl)ethyl)methyl carbamic acid tert-butylester.

Workup

  1. additionadded
  2. stirringThe reaction mixture was stirred for 48 hours
  3. washThe reaction was washed with water (30 mL)
  4. dry with materialan aqueous solution of sodium hydrogen sulfate (10%; 30 mL), an aqueous solution of sodium hydrogen carbonate (saturated; 30 mL) and dried (magnesium sulfate)
  5. customThe solvent was removed in vacuo
  6. customthe residue was chromatographed on silica (3×30 cm)

Sources & evidence

ORD record
ord-8b810e1fc7cf4eab90926dd67a39d425
Source dataset
uspto-grants-1999_11
Patent number
US05977178

Reaction notes

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