Triethylamine → n-(4-Bromo-3-methylisothiazol-5-yl)hexahydro-2,5-methanopentalene-3a(1h)-carboxamide

HRID 76249Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 76249
[Br:1][C:2]1[C:3]([CH3:8])=[N:4][S:5][C:6]=1[NH2:7].C(N(CC)CC)C.[CH2:16]1[CH:23]2[C:19]3([C:25](Cl)=[O:26])[CH2:20][CH:21]([CH2:24][CH:17]1[CH2:18]3)[CH2:22]2>O1CCCC1>[Br:1][C:2]1[C:3]([CH3:8])=[N:4][S:5][C:6]=1[NH:7][C:25]([C:19]12[CH2:20][CH:21]3[CH2:24][CH:17]([CH2:16][CH:23]1[CH2:22]3)[CH2:18]2)=[O:26]

Komponenten

5

Edukt 3

HCID 8471TriethylamineHCID 13182402Hexahydro-2,5-methano-pentalene-3a-carbonyl chlorideHCID 177499314-Bromo-3-methyl-1,2-thiazol-5-amine

Produkt 1

HCID 66867944n-(4-Bromo-3-methylisothiazol-5-yl)hexahydro-2,5-methanopentalene-3a(1h)-carboxamideAusbeute 8,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

To a solution of 4-bromo-3-methylisothiazol-5-amine (prepared as described in J. Chem. Soc. 1963, p 2032) (1.93 g, 10.1 mmol) in tetrahydrofuran (25 mL) with triethylamine (1.7 mL, 12.2 mmol) at 0° C. was added slowly a solution of Example 4A (1.9 g, 10.3 mmol) in tetrahydrofuran (15 mL). The reaction was allowed to warm to room temperature and stirred overnight. The reaction was evaporated to dryness, partitioned between H2O/ethyl acetate and the aqueous extracted again (2×) with ethyl acetate. The organics were combined, dried (MgSO4), filtered and solvent evaporated. Flash chromatography over silica gel eluting with 15% ethyl acetate/hexane provided 0.3 g of the title compound plus 1.8 g of diacylated compound. The latter was heated to reflux in methanol for 3 h, cooled, solvent evaporated and flash chromatographed over silica gel eluting with 20% ethyl acetate/hexane to provide an additional 0.99 g of the title compound. 1H NMR (300 MHz, CDCl3) δ 1.63-1.76 (m, 4H), 1.87-1.98 (m, 4H), 2.10-2.15 (m, 2H), 2.45 (s, 3H), 2.81 (t, 1H), 8.23 (br s, 1H).

Aufarbeitung

  1. customThe reaction was evaporated to dryness
  2. custompartitioned between H2O/ethyl acetate
  3. extractionthe aqueous extracted again (2×) with ethyl acetate
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customsolvent evaporated

Quellen und Nachweise

ORD-Eintrag
ord-5f218ddf7b45437bb2d68c60e10d2663
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08835475B2

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