Diisopropylethylamine → 2-((2R)-2-(N-((2R)-2-(N-tert-Butoxycarbonyl-N-methylamino)-3-(2-naphthyl) propionyl)-N-methylamino)-3-phenylpropionylamino)-1,1-dimethylethyl acetate

HRID 495806Notes

Reaction equation

HRID 495806 reaction equation
[C:1]([O:5][C:6]([N:8]([C@H:10]([CH2:14][C:15]1[CH:24]=[CH:23][C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:16]=1)[C:11](O)=[O:12])[CH3:9])=[O:7])([CH3:4])([CH3:3])[CH3:2].ON1C2N=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[C:47]([O:50][C:51]([CH3:67])([CH3:66])[CH2:52][NH:53][C:54](=[O:65])[C@H:55]([NH:63][CH3:64])[CH2:56][C:57]1[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=1)(=[O:49])[CH3:48].C(N(C(C)C)C(C)C)C>CN(C)C=O.ClCCl.C(OCC)(=O)C>[C:47]([O:50][C:51]([CH3:67])([CH3:66])[CH2:52][NH:53][C:54](=[O:65])[C@H:55]([N:63]([C:11](=[O:12])[C@H:10]([N:8]([C:6]([O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[O:7])[CH3:9])[CH2:14][C:15]1[CH:24]=[CH:23][C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:16]=1)[CH3:64])[CH2:56][C:57]1[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=1)(=[O:49])[CH3:48]

Participants

9

Reactant 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10065151(2R)-2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]-3-naphthalen-2-ylpropanoic acidHCID 541776851,1-dimethyl-2-((2R)-2-methylamino-3-phenylpropionylamino)ethyl acetate

Product 1

HCID 541114972-((2R)-2-(N-((2R)-2-(N-tert-Butoxycarbonyl-N-methylamino)-3-(2-naphthyl) propionyl)-N-methylamino)-3-phenylpropionylamino)-1,1-dimethylethyl acetateYield 88%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

(2R)-2-(N-(tert-Butoxycarbonyl)-N-methylamino)-3-(2-naphthyl)propionic acid (373 mg, 1.13 mmol) was dissolved in N,N-dimethylformamide (2 ml) and dichloromethane (2 ml). 1-Hydroxy-7-azabenzotriazole (153 mg, 1.13 mmol) was added. The solution was cooled to 0° C. N-(3-Dimethylaminopropyl)-N′-ethyl-carbodiimide hydrochloride (217 mg, 1.13 mmol) was added. The reaction mixture was stirred for 10 min at 0° C. 1,1-Dimethyl-2-((2R)-2-methylamino-3-phenylpropionylamino)-ethyl acetate (301 mg, 1.03 mmol) was dissolved in is dichloromethane (2 ml) and added. Ethyldiisopropylamine (0.18 ml, 1.03 mmol) was added. The reaction mixture was stirred for 20 h, while it was warming up to room temperature. It was diluted with ethyl acetate (100 ml) and washed with 1 N hydrochloric acid. The aqueous phase was extracted with ethyl acetate (3×30 ml). The combined organic layers were washed with saturated sodium hydrogen carbonate solution (100 ml) and dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (85 g), using ethyl acetatelheptane (1:1) as eluent, to give 547 mg of 2-((2R)-2-(N-((2R)-2(N-tert-butoxycarbonyl-N-methylamino)-3-(2-naphthyl)propionyl)-N-methylamino)-3-phenylpropionylamino)-1,1-dimethylethyl acetate.

Workup

  1. additionadded
  2. stirringThe reaction mixture was stirred for 20 h, while it
  3. temperaturewas warming up to room temperature
  4. washwashed with 1 N hydrochloric acid
  5. extractionThe aqueous phase was extracted with ethyl acetate (3×30 ml)
  6. washThe combined organic layers were washed with saturated sodium hydrogen carbonate solution (100 ml)
  7. dry with materialdried over magnesium sulfate
  8. customThe solvent was removed in vacuo
  9. customThe crude product was purified by flash chromatography on silica (85 g)

Sources & evidence

ORD record
ord-44e35e16a9db4ea9a37dab195513ba8a
Source dataset
uspto-grants-2005_09
Patent number
US06939880B2

Reaction notes

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