Diisopropylethylamine → Benzyl 4-(1-(2-(benzyloxy)-2-oxoethyl)cyclopentylamino)-2-(biphenyl-4-ylmethyl)-4-oxobutanoate

HRID 333307Notes

Reaction equation

HRID 333307 reaction equation
Cl.[NH2:2][C:3]1([CH2:8][C:9]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:10])[CH2:7][CH2:6][CH2:5][CH2:4]1.[CH2:19]([O:26][C:27](=[O:46])[CH:28]([CH2:33][C:34]1[CH:39]=[CH:38][C:37]([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)=[CH:36][CH:35]=1)[CH2:29][C:30](O)=[O:31])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.CCN=C=NCCCN(C)C.Cl.ON1C2N=CC=CC=2N=N1.CCN(C(C)C)C(C)C>CN(C=O)C>[CH2:12]([O:11][C:9](=[O:10])[CH2:8][C:3]1([NH:2][C:30](=[O:31])[CH2:29][CH:28]([CH2:33][C:34]2[CH:35]=[CH:36][C:37]([C:40]3[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=3)=[CH:38][CH:39]=2)[C:27]([O:26][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[O:46])[CH2:7][CH2:6][CH2:5][CH2:4]1)[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 68749504Benzyl 2-(1-aminocyclopentyl)acetate hydrochlorideHCID 687501454-(Benzyloxy)-3-(biphenyl-4-ylmethyl)-4-oxobutanoic acid

Product 1

HCID 68751041Benzyl 4-(1-(2-(benzyloxy)-2-oxoethyl)cyclopentylamino)-2-(biphenyl-4-ylmethyl)-4-oxobutanoateYield 75.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of benzyl 2-(1-aminocyclopentyl)acetate hydrochloride (66 mg, 0.245 mmol), 4-(benzyloxy)-3-(biphenyl-4-ylmethyl)-4-oxobutanoic acid (78 mg, 0.209 mmol), WSC.HCl (60.1 mg, 0.314 mmol) and 1-hydroxy-7-azabenzotriazole (42.7 mg, 0.314 mmol) in DMF (2 ml) was added DIPEA (0.055 ml, 0.314 mmol) at room temperature. After stirred for 4 hours, the reaction was quenched with H2O. The product was extracted with EtOAc, and the organic layer was washed with brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The obtained residue was purified by flash column chromatography on silica gel (eluent: heptane/EtOAc=100:0 to 0:100) to give benzyl 4-(1-(2-(benzyloxy)-2-oxoethyl)cyclopentylamino)-2-(biphenyl-4-ylmethyl)-4-oxobutanoate (93 mg); Retention time=1.85 minutes (condition B); MS (m+1)=590.3; 1H NMR (400 MHz, CDCl3, mixture of rotamers) δ ppm 1.61-1.72 (m, 6H) 1.96-2.06 (m, 2H) 2.17-2.46 (m, 2H) 2.81-3.00 (m, 4H) 3.22-3.29 (m, 1H) 5.02-5.12 (m, 4H) 5.62 (br s, 1H) 7.15-7.57 (m, 19H).

Workup

  1. customthe reaction was quenched with H2O
  2. extractionThe product was extracted with EtOAc
  3. washthe organic layer was washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe obtained residue was purified by flash column chromatography on silica gel (eluent: heptane/EtOAc=100:0 to 0:100)

Sources & evidence

ORD record
ord-e094fd15efdf4a0b913cb90719f33af2
Source dataset
uspto-grants-2014_11
Patent number
US08877815B2

Reaction notes

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