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

HRID 76249ノート

反応式

HRID 76249 の反応式
[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]

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-5f218ddf7b45437bb2d68c60e10d2663
出典データセット
uspto-grants-2014_09
特許番号
US08835475B2

反応ノート

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