Dicyclohexylcarbodiimide → (2R)-2-[N-(4-Chlorobenzenesulfonyl)-N-(cyclopropylcarbamoylmethyl)amino]-4-methyl-pentanoic acid amide

HRID 1893837Notes

Reaction equation

HRID 1893837 reaction equation
[C:1]([C@H:4]([N:9]([CH2:20][C:21]([OH:23])=O)[S:10]([C:13]1[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=1)(=[O:12])=[O:11])[CH2:5][CH:6]([CH3:8])[CH3:7])(=[O:3])[NH2:2].[CH:24]1([NH2:27])[CH2:26][CH2:25]1.ON1C2C=CC=CC=2N=N1.C1(N=C=NC2CCCCC2)CCCCC1>C(Cl)Cl.CCOC(C)=O.O>[Cl:19][C:16]1[CH:17]=[CH:18][C:13]([S:10]([N:9]([C@H:4]([CH2:5][CH:6]([CH3:7])[CH3:8])[C:1]([NH2:2])=[O:3])[CH2:20][C:21](=[O:23])[NH:27][CH:24]2[CH2:26][CH2:25]2)(=[O:11])=[O:12])=[CH:14][CH:15]=1

Participants

7

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 69828CyclopropylamineHCID 757711-HydroxybenzotriazoleHCID 59001083{N-[(1R)-1-Carbamoyl-3-methyl-butyl]-N-(4-chlorobenzenesulfonyl)amino}acetic acid

Product 1

HCID 59001091(2R)-2-[N-(4-Chlorobenzenesulfonyl)-N-(cyclopropylcarbamoylmethyl)amino]-4-methyl-pentanoic acid amideYield 29%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 22728543Water ethylacetateSolvent

Procedure

To a solution of {N-[(1R)-1-carbamoyl-3-methyl-butyl]-N-(4-chlorobenzenesulfonyl)amino}acetic acid (Example 59, 175 mg, 0.480 mmol), cyclopropylamine (41 mL, 0.58 mmol) in CH2Cl2 (3 mL) was added 1-hydroxybenzotriazole (47 mg, 0.72 mmol), and 1,3-dicyclohexylcarbodiimide (144 mg, 0.720 mmol). The reaction was stirred for 18 h at rt, and then was poured into an EtOAc/water mixture. The organic layer was separated, dried over MgSO4, and concentrated to a clear oil residue. The residue was further purified by BIOTAGE® 40S (eluted in 40% EtOAc in hexanes) to afford a white solid (54 mg, 29%). MS (ESI), (M+H)+402.2; 1H NMR (CDCl3, 500 MHz) δ 7.85 (dd, 2H, J=1.9, 8.9), 7.50 (dd, 2H, J=2.0, 8.7), 7.40 (br s, 1H), 6.55 (br s, 1H), 6.30 (br s, 1H), 4.23 (dd, 1H, J=2.9, 8.9), 3.92 (d, 1H, J=17), 3.83 (d, 1H, J=17), 2.68-2.73 (m, 1H), 1.75-1.83 (m, 1H), 1.50-1.57 (m, 1H), 1.40-1.49 (m, 1H), 0.88 (d, 3H, J=6.4), 0.87 (d, 3H, J=6.7), 0.80 (d, 2H, J=7.0), 0.51 (t, 2H, J=4.0).

Workup

  1. customThe organic layer was separated
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated to a clear oil residue
  4. customThe residue was further purified by BIOTAGE® 40S (eluted in 40% EtOAc in hexanes)

Sources & evidence

ORD record
ord-97587063e8e04eaab0f9b13b44228e0c
Source dataset
uspto-grants-2013_08
Patent number
US08513253B2

Reaction notes

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