1,2-Dichloroethane → HCID 58802355, Verbindung

HRID 14290Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 14290
[CH2:1]([N:4]([CH2:21][CH2:22][CH3:23])[C:5]([C:7]1[CH:8]=[C:9]([CH:13]=[C:14]([C:16]2[S:17][CH:18]=[CH:19][N:20]=2)[CH:15]=1)[C:10]([OH:12])=O)=[O:6])[CH2:2][CH3:3].Cl.Cl.[NH2:26][C@@H:27]([CH2:41][C:42]1[CH:47]=[C:46]([F:48])[CH:45]=[C:44]([F:49])[CH:43]=1)[C@H:28]([OH:40])[CH2:29][NH:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([CH2:38][CH3:39])[CH:33]=1.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.C(Cl)CCl>CN(C)C=O.O>[F:48][C:46]1[CH:47]=[C:42]([CH:43]=[C:44]([F:49])[CH:45]=1)[CH2:41][C@H:27]([NH:26][C:10](=[O:12])[C:9]1[CH:13]=[C:14]([C:16]2[S:17][CH:18]=[CH:19][N:20]=2)[CH:15]=[C:7]([C:5]([N:4]([CH2:21][CH2:22][CH3:23])[CH2:1][CH2:2][CH3:3])=[O:6])[CH:8]=1)[C@H:28]([OH:40])[CH2:29][NH:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([CH2:38][CH3:39])[CH:33]=1

Komponenten

8

Edukt 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 210857833-[(Dipropylamino)carbonyl]-5-(1,3-thiazol-2-yl)benzoic AcidHCID 57487281(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol dihydrochloride

Produkt 1

HCID 58802355HCID 58802355, VerbindungAusbeute 10,8 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

A solution of 3-[(dipropylamino)carbonyl]-5-(1,3-thiazol-2-yl)benzoic acid (156 mg, 0.47 mmol), (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol dihydrochloride (191 mg, 0.47 mmol), HOBt (64 mg, 0.47 mmol), and N-methylmorpholine (200 μL, 1.5 mmol) was stirred in dimethylformamide (2 mL) for 15 min. EDC (145 mg, 0.84 mmol) was added and the reaction mixture was stirred overnight. The reaction mixture was diluted with water, and extracted with ethyl acetate (3×25 mL). The organic layer was washed with 1 N hydrochloric acid (25 mL), saturated sodium bicarbonate (25 mL), saturated sodium chloride, dried (sodium sulfate), and concentrated under reduced pressure. Purification by flash column chromatography (silica, 1:9 methanol/chloroform) provided N1-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N3,N3-dipropyl-5-(1,3-thiazol-2-yl)isophthalamide (33 mg): 1H NMR (500 MHz, CDCl3) δ 8.40 (br s, 1H, —NH), 8.15 (br s, 1H), 7.94 (br s, 1H), 7.80 (d, J=3 Hz, 1H), 7.51 (br s, 1H), 7.34 (d, J=3 Hz, 1H), 7.27-7.24 (m, 1H), 7.21-7.18 (m, 2H), 7.11-7.10 (m, 1H), 7.00 (br s, 1H), 6.62-6.58 (m, 1H), 4.23 (d, J=5 Hz, 1H), 3.91-3.85 (m, 3H), 3.57 (br s, 2H), 3.31 (br s, 2H), 3.05 (d, J=5 Hz, 4H), 2.83 (d, , J=6 Hz, 2H), 2.64 (q, J=8 Hz, 2H), 1.75 (br s, 2H), 1.44 (t, J=7 Hz, 2H), 1.22 (t, J=8 Hz, 3H) 1.04 (t, J=7 Hz, 3H), 0.65 (t, J=7 Hz, 3H); ESI MS m/z 649 [M+H]+;

Aufarbeitung

  1. extractionextracted with ethyl acetate (3×25 mL)
  2. washThe organic layer was washed with 1 N hydrochloric acid (25 mL), saturated sodium bicarbonate (25 mL), saturated sodium chloride
  3. dry with materialdried (sodium sulfate)
  4. concentrationconcentrated under reduced pressure
  5. customPurification by flash column chromatography (silica, 1:9 methanol/chloroform)

Quellen und Nachweise

ORD-Eintrag
ord-dce0dc0174f747f187dfec5ee21f828c
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07727997B2

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