1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 59607868, compound

HRID 70828Notes

Reaction equation

HRID 70828 reaction equation
Cl.[NH2:2][C@H:3]([CH2:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([Cl:28])[CH:23]=2)=[CH:18][CH:17]=1)[CH2:4][C:5]([O:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:6].[CH2:29]([O:33][C:34](=[O:40])[CH2:35][CH2:36][C:37](O)=[O:38])[CH2:30][CH2:31][CH3:32].CCN=C=NCCCN(C)C.CCN(C(C)C)C(C)C.C1C=NC2N(O)N=NC=2C=1>CN(C=O)C.O>[CH2:29]([O:33][C:34](=[O:40])[CH2:35][CH2:36][C:37]([NH:2][C@H:3]([CH2:15][C:16]1[CH:17]=[CH:18][C:19]([C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([Cl:28])[CH:23]=2)=[CH:20][CH:21]=1)[CH2:4][C:5]([O:7][CH2:8][C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1)=[O:6])=[O:38])[CH2:30][CH2:31][CH3:32]

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 78829Butanedioic acid, 1-butyl esterHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 86648193(R)-benzyl 3-amino-4-(3'-chlorobiphenyl-4-yl)butanoate hydrochloride

Product 1

HCID 59607868HCID 59607868, compoundYield 92.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of (R)-benzyl 3-amino-4-(3′-chlorobiphenyl-4-yl)butanoate hydrochloride (150 mg, 0.360 mmol), 4-butoxy-4-oxobutanoic acid (107 mg, 0.540 mmol, 88% purity), EDCI (104 mg, 0.540 mmol), DIPEA (0.094 ml, 0.540 mmol) and HOAt (73.6 mg, 0.540 mmol) in DMF (2 ml) is allowed to stir at room temperature for 1 hour. The reaction mixture is diluted with water, and then the precipitated solid is collected on a funnel, washed with H2O, and dried under reduced pressure to give crude. The obtained residue is purified by silica gel flash column chromatography (heptane/EtOAc=100:0 to 0:100) to give (R)-benzyl 3-(4-butoxy-4-oxobutanamido)-4-(3′-chlorobiphenyl-4-yl)butanoate (178.9 mg); HPLC retention time=1.47 minutes (condition B); MS (m+1)=536.42; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.90-0.94 (m, 3 H) 1.31-1.40 (m, 2 H) 1.56-1.63 (m, 2 H) 2.39-2.42 (m, 2 H) 2.48-2.62 (m, 4 H) 2.84 (A of ABX, Jab=13.6 Hz, Jax=8.1 Hz, 1 H) 2.97 (B of ABX, Jab=13.6 Hz, Jbx=6.6 Hz, 1 H) 4.07 (t, J=6.7 Hz, 2 H) 4.48-4.56 (m, 1 H) 5.12 (A of AB, J=12.1 Hz, 1 H) 5.18 (B of AB, J=12.1 Hz, 1 H) 6.27 (br d, J=7.7 Hz, 1 H) 7.20 (d, J=8.3 Hz, 1 H) 7.29-7.39 (m, 7 H) 7.42-7.47 (m, 3 H) 7.54-7.55 (m, 1 H).

Workup

  1. customthe precipitated solid is collected on a funnel
  2. washwashed with H2O
  3. customdried under reduced pressure
  4. customto give crude
  5. customThe obtained residue is purified by silica gel flash column chromatography (heptane/EtOAc=100:0 to 0:100)

Sources & evidence

ORD record
ord-a5d42b0fa5a94bf2a6c108e895aef898
Source dataset
uspto-grants-2014_09
Patent number
US08822534B2

Reaction notes

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