1,2-Dichloroethane → HCID 178444059, Verbindung

HRID 1775799Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1775799
[C:1]([C:5]1[CH:28]=[CH:27][C:8]([C:9]([NH:11][C@H:12]([C:23]([O:25][CH3:26])=[O:24])[CH2:13][C:14]2[CH:22]=[CH:21][C:17]([C:18]([OH:20])=[O:19])=[CH:16][CH:15]=2)=[O:10])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.[CH2:43]([O:50][C:51]1[CH:60]=[CH:59][C:54](/[C:55](=[N:57]/O)/[NH2:56])=[CH:53][CH:52]=1)[CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH3:49]>CN(C=O)C>[C:1]([C:5]1[CH:28]=[CH:27][C:8]([C:9]([NH:11][C@@H:12]([CH2:13][C:14]2[CH:15]=[CH:16][C:17]([C:18]([O:20][NH:57][C:55](=[NH:56])[C:54]3[CH:53]=[CH:52][C:51]([O:50][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH3:49])=[CH:60][CH:59]=3)=[O:19])=[CH:21][CH:22]=2)[C:23]([O:25][CH3:26])=[O:24])=[O:10])=[CH:7][CH:6]=1)([CH3:4])([CH3:2])[CH3:3]

Komponenten

6

Edukt 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 431283004-heptoxy-N'-hydroxybenzenecarboximidamideHCID 86689655(S)-4-(2-(4-(tert-butyl)benzamido)-3-methoxy-3-oxopropyl)benzoic acid

Produkt 1

HCID 178444059HCID 178444059, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

Prepared using General Procedure 5: To a solution of (S)-4-(2-(4-(tert-butyl)benzamido)-3-methoxy-3-oxopropyl)benzoic acid, INT-1 (10.0 mg, 0.026 mmol) in anhydrous DMF (1 mL) was added HOBt (5.27 mg, 0.39 mmol) and EDC (7.48 mg, 0.39 mmol). After stirring for 2 h, (Z)-4-(heptyloxy)-N′-hydroxybenzimidamide (9.76 mg, 0.39 mmol) was added. The reaction mixture was stirred at room temperature for 2 h, partitioned between saturated aqueous NaHCO3 (5 ml) and EA (5 mL), and concentrated under reduced pressure to afford the intermediate (5)-methyl 2-(4-(tert-butyl)benzamido)-3-(4-(((4-(heptyloxy)benzimidamido) oxy)carbonyl)phenyl)propanoate. The intermediate was dissolved in DMF (1 mL) and heated to 100° C. for 18 h. The reaction mixture was cooled to room temperature and partitioned between EA (5 mL) and saturated aqueous NaHCO3 (5 mL). The organic layer was extracted with water (2×5 mL) and brine (5 mL). The organic layer was dried over MgSO4 and concentrated. The brown oil was purified by preparative HPLC to afford 4.5 mg (29%) of (5)-methyl 2-(4-(tert-butyl)benzamido)-3-(4-(3-(4-(heptyloxy)phenyl)-1,2,4-oxadiazol-5-yl)phenyl)propanoate. LCMS-ESI (m/z) calculated for C36H43N3O5: 597.3; no m/z observed, tR=12.75 min (Method 2). 1H NMR (400 MHz, DMSO) δ 8.85 (d, J=8.0 Hz, 1H), 8.09 (d, J=8.3 Hz, 2H), 8.00 (d, J=8.9 Hz, 2H), 7.74 (d, J=8.5 Hz, 2H), 7.59 (d, J=8.4 Hz, 2H), 7.48 (d, J=8.6 Hz, 2H), 7.12 (d, J=8.9 Hz, 2H), 4.87-4.56 (m, 1H), 4.06 (t, J=6.5 Hz, 2H), 3.67 (s, 3H), 3.32-3.13 (m, 4H), 1.74 (dd, J=14.2, 6.5 Hz, 2H), 1.51-1.37 (m, 2H), 1.33 (s, 4H), 1.26 (d, J=20.2 Hz, 9H), 0.88 (t, J=6.9 Hz, 3H). 13C NMR (101 MHz, DMSO) δ 175.00, 171.91, 167.89, 166.27, 161.21, 154.37, 143.68, 130.78, 130.30, 128.76, 127.80, 127.18, 125.07, 121.69, 118.21, 115.07, 67.72, 53.61, 52.05, 36.15, 34.60, 31.20, 30.87, 28.54, 28.39, 25.40, 22.02, 13.93.

Aufarbeitung

  1. customPrepared
  2. stirringThe reaction mixture was stirred at room temperature for 2 h
  3. custompartitioned between saturated aqueous NaHCO3 (5 ml) and EA (5 mL)
  4. concentrationconcentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-c603ce629c384aa99395a944538bdbf6
Quelldatensatz
uspto-grants-2016_02
Patentnummer
US09260427B2

Notizen zur Reaktion

Wird geladen…