Diisopropylethylamine → HCID 68567290, compound

HRID 1865434Notes

Reaction equation

HRID 1865434 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:13]=[C:12]([C:14]3[CH:15]=[C:16]4[C:21](=[CH:22][CH:23]=3)[N:20]=[CH:19][CH:18]=[N:17]4)[N:11]([CH:24]([C:26]3[CH:34]=[CH:33][C:29]([C:30](O)=[O:31])=[CH:28][CH:27]=3)[CH3:25])[N:10]=2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.Cl.[NH2:36][CH2:37][CH2:38][C:39]([O:41][CH2:42][CH3:43])=[O:40].ON1C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.Cl.CN(C)CCCN=C=NCC>CN(C=O)C.CCOC(C)=O>[Cl:8][C:6]1[CH:5]=[C:4]([C:9]2[CH:13]=[C:12]([C:14]3[CH:15]=[C:16]4[C:21](=[CH:22][CH:23]=3)[N:20]=[CH:19][CH:18]=[N:17]4)[N:11]([CH:24]([C:26]3[CH:27]=[CH:28][C:29]([C:30]([NH:36][CH2:37][CH2:38][C:39]([O:41][CH2:42][CH3:43])=[O:40])=[O:31])=[CH:33][CH:34]=3)[CH3:25])[N:10]=2)[CH:3]=[C:2]([Cl:1])[CH:7]=1

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 458475beta-Alanine, ethyl ester, hydrochlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 67487982HCID 67487982, compound

Product 1

HCID 68567290HCID 68567290, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of the intermediate from step G (39.7 mg, 0.08 mmol) in 3 mL of anhydrous DMF was added ethyl β-alaninate hydrochloride (19 mg, 0.12), 1-hydroxy-7-azabenzo-triazole (17 mg, 0.12 mmol), N,N-diisopropylethyl amine (0.04 mL, 0.24 mmol), and 1-[3-(dimethylamino)propyl]-3-ethyl carbodiimide hydrochloride (24 mg, 0.12 mmol). The reaction was left stirring at room temperature for 12 hours then diluted with EtOAc and washed with 1N HCl (2×), saturated sodium bicarbonate (2×), and brine (1×). The organic layer was then dried over anhydrous MgSO4, filtered and concentrated in vacuo. The resulting solid was purified by flash chromatography (30% EtOAc/Hexanes) to afford a light yellow solid. Enantiomers were then separated using SFC-HPLC semi-prep methodology with the conditions as follows: column=ChiralCel OJ 10×250 mm 10 micron, flow rate=10.0 mL/min, mobile Phase=40% MeOH (0.1% TFA)/CO2, column temperature=40° C., UV wavelength=248 nm, outlet pressure=100 bar, concentration=50 mg/mL in MeOH. Retention time: Isomer A=4.03 min; Isomer B=5.01 min. LC-MS: 4.20 min. (M+H)=589.48.

Workup

  1. waitThe reaction was left
  2. washwashed with 1N HCl (2×), saturated sodium bicarbonate (2×), and brine (1×)
  3. dry with materialThe organic layer was then dried over anhydrous MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe resulting solid was purified by flash chromatography (30% EtOAc/Hexanes)
  7. customto afford a light yellow solid
  8. customEnantiomers were then separated
  9. customcolumn=ChiralCel OJ 10×250 mm 10 micron, flow rate=10.0 mL/min, mobile Phase=40% MeOH (0.1% TFA)/CO2, column temperature=40° C., UV wavelength=248 nm, outlet pressure=100 bar, concentration=50 mg/mL in MeOH
  10. customA=4.03 min
  11. customIsomer B=5.01 min
  12. custom4.20 min. (M+H)=589.48

Sources & evidence

ORD record
ord-29c76783e6ca48c6b4c2b11eb7f18b04
Source dataset
uspto-grants-2009_12
Patent number
US07625938B2

Reaction notes

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