Diisopropylethylamine → HCID 70122446, compound

HRID 333303Notes

Reaction equation

HRID 333303 reaction equation
[C:1]1([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH:6]=[CH:5][C:4]([CH2:7][C@H:8]([NH:12][C:13]([C:15]2([CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH2:19][CH2:18][CH2:17][CH2:16]2)=[O:14])[C:9]([OH:11])=O)=[CH:3][CH:2]=1.Cl.[NH:33]1[CH2:37][CH2:36][CH2:35][C@H:34]1[C:38]([O:40][CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)=[O:39].CCN=C=NCCCN(C)C.Cl.CCN(C(C)C)C(C)C.ON1C2N=CC=CC=2N=N1>CN(C=O)C>[C:1]1([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH:2]=[CH:3][C:4]([CH2:7][C@H:8]([NH:12][C:13]([C:15]2([CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH2:16][CH2:17][CH2:18][CH2:19]2)=[O:14])[C:9]([N:33]2[CH2:37][CH2:36][CH2:35][C@H:34]2[C:38]([O:40][CH2:41][C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)=[O:39])=[O:11])=[CH:5][CH:6]=1

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2733413Proline benzyl ester hydrochlorideHCID 68751577HCID 68751577, compound

Product 1

HCID 70122446HCID 70122446, compoundYield 83.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of (S)-3-(biphenyl-4-yl)-2-(1-(2-ethoxy-2-oxoethyl)cyclopentanecarboxamido)propanoic acid (201.7 mg, 0.476 mmol), (S)-benzyl pyrrolidine-2-carboxylate hydrochloride (138 mg, 0.572 mmol), WSC.HCl (137 mg, 0.714 mmol), DIPEA (0.125 ml, 0.714 mmol) and 1-hydroxy-7-azabenzotriazole (97 mg, 0.714 mmol) in DMF (2 ml) was allowed to stir at room temperature under nitrogen for 14 hours. The reaction was quenched with H2O. The products were extracted with EtOAc. The organic layer was washed with NH4Claq, 0.1 M HCl (twice) and then brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The obtained residue was purified by flash column chromatography on silica gel (heptane/EtOAc=100:0 to 0:100) to give (S)-benzyl 1-((S)-3-(biphenyl-4-yl)-2-(1-(2-ethoxy-2-oxoethyl)cyclopentanecarboxamido)propanoyl)pyrrolidine-2-carboxylate (243 mg); Retention time=1.74 minutes (condition B); MS (m+1)=611.2; 1H NMR (400 MHz, CD3CN, mixture of rotamers) δ ppm 0.91-1.06 (m, 3H) 1.33-1.42 (m, 6H) 1.55-2.09 (m, 6H) 2.25-2.42 (m, 2H) 2.57-2.93 (m, 2H) 3.06-3.59 (m, 2H) 3.75-3.91 (m, 2H) 4.14-4.61 (m, 2H) 4.68-5.09 (m, 3H) 6.40-6.52 (m, 1H) 7.00-7.45 (m, 14H).

Workup

  1. customThe reaction was quenched with H2O
  2. extractionThe products were extracted with EtOAc
  3. washThe organic layer was washed with NH4Claq, 0.1 M HCl (twice) and then 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 (heptane/EtOAc=100:0 to 0:100)

Sources & evidence

ORD record
ord-9857fa9864cf4ef89e44a2ebe7bc8ef2
Source dataset
uspto-grants-2014_11
Patent number
US08877815B2

Reaction notes

Loading…