Diisopropylethylamine → HCID 21025143, Verbindung

HRID 1796618Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1796618
[CH3:1][O:2][C:3]([C:5]1[C:6]([CH3:41])=[C:7]2[C:12]([NH:13][C:14]3[CH:19]=[CH:18][C:17]([O:20][C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=4[O:27][C:28]([C:31](OC(C)(C)C)=[O:32])([CH3:30])[CH3:29])=[CH:16][CH:15]=3)=[C:11]([C:38]#[N:39])[CH:10]=[N:9][N:8]2[CH:40]=1)=[O:4].Cl.[C:43]([O:47][C:48](=[O:51])[CH2:49][NH2:50])([CH3:46])([CH3:45])[CH3:44].CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C.Cl>C(O)(C(F)(F)F)=O.C(Cl)Cl.O.ClCCCl.CN(C1C=CN=CC=1)C>[CH3:1][O:2][C:3]([C:5]1[C:6]([CH3:41])=[C:7]2[C:12]([NH:13][C:14]3[CH:15]=[CH:16][C:17]([O:20][C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=4[O:27][C:28]([C:31](=[O:32])[NH:50][CH2:49][C:48]([O:47][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:51])([CH3:30])[CH3:29])=[CH:18][CH:19]=3)=[C:11]([C:38]#[N:39])[CH:10]=[N:9][N:8]2[CH:40]=1)=[O:4]

Komponenten

8

Edukt 4

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2725036Glycine tert-butyl ester hydrochlorideHCID 22179696HCID 22179696, Verbindung

Produkt 1

HCID 21025143HCID 21025143, VerbindungAusbeute 70 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 111,2-DichloroethaneLösungsmittelHCID 18672661TFA dichloromethane waterLösungsmittel

Versuchsvorschrift

A solution of ester 388D (482 mg, 0.866 mmol) in TFA/CH2Cl2/H2O (5 ml, 48/48/4) was stirred for 1 h at rt, concentrated, the resulting residue was rotavaped with chloroform twice and CH2Cl2 once to give acid intermediate as a yellow solid. The solid was dissolved in 1,2-dichloroethane (5 ml), glycine t-butyl ester hydrochloride (203 mg, 1.21 mmol), DMAP (52.9 mg, 0.433 mmol) and DIEA (528 μl, 3.03 mmol) were added. The mixture was stirred 3 min until homogeneous, then EDC.HCl (249 mg, 1.30 mmol) was added. The reaction mixture was stirred for 2 h, concentrated, partitioned between EtOAc (50 ml) and 1N HCl (50 ml). The organic layer were washed with 1N HCl (30 ml), the combined aqueous wash layer was extracted with EtOAc (3×50 ml), the combined organic layer was washed with brine (100 ml), dried with Na2SO4 and concentrated. The residue was purified by silica gel flash column chromatography to afford a yellow crystalline solid 388 (372 mg, 70%)(10%-25% EtOAc—CH2Cl2). LCMS Found: (M+H)+=613.6; (M−tBu+2H)+=558.2

Aufarbeitung

  1. concentrationconcentrated
  2. customCH2Cl2 once to give acid intermediate as a yellow solid
  3. additionwas added
  4. concentrationconcentrated
  5. custompartitioned between EtOAc (50 ml) and 1N HCl (50 ml)
  6. washThe organic layer were washed with 1N HCl (30 ml)
  7. extractionthe combined aqueous wash layer was extracted with EtOAc (3×50 ml)
  8. washthe combined organic layer was washed with brine (100 ml)
  9. dry with materialdried with Na2SO4
  10. concentrationconcentrated
  11. customThe residue was purified by silica gel flash column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-83e95122e4484718966b9377ec0ec04e
Quelldatensatz
uspto-grants-2006_04
Patentnummer
US07030112B2

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