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

HRID 253611Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 253611
[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-1474e25412834ca4a213b804d184a9a3
Quelldatensatz
uspto-grants-2011_01
Patentnummer
US07872033B2

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