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

HRID 1888621Notes

Reaction equation

HRID 1888621 reaction equation
[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]

Participants

5

Reactant 3

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

Product 1

HCID 66867944n-(4-Bromo-3-methylisothiazol-5-yl)hexahydro-2,5-methanopentalene-3a(1h)-carboxamideYield 8.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

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 ppm 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).

Workup

  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

Sources & evidence

ORD record
ord-b2fe1e86840f4e459377213b3aabc1ee
Source dataset
uspto-grants-2013_08
Patent number
US08501794B2

Reaction notes

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