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

HRID 253611노트

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HRID 253611 반응식
[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]

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-1474e25412834ca4a213b804d184a9a3
출처 데이터셋
uspto-grants-2011_01
특허 번호
US07872033B2

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