Ethanolamine → HCID 57664575、化合物

HRID 1467897ノート

反応式

HRID 1467897 の反応式
[CH:1]1([N:4]([CH:18]2[CH2:23][CH2:22][N:21]([C:24](=[O:30])[CH:25]=[CH:26][CH2:27][CH2:28][CH3:29])[CH2:20][CH2:19]2)[S:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:16])[F:15])[CH:9]=2)(=[O:7])=[O:6])[CH2:3][CH2:2]1.[CH2:31]([CH2:33][NH2:34])[OH:32]>>[CH:1]1([N:4]([CH:18]2[CH2:23][CH2:22][N:21]([C:24](=[O:30])[CH2:25][CH:26]([NH:34][CH2:33][CH2:31][OH:32])[CH2:27][CH2:28][CH3:29])[CH2:20][CH2:19]2)[S:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:15])([F:16])[F:17])[CH:9]=2)(=[O:6])=[O:7])[CH2:3][CH2:2]1

参加物

3

反応物 2

HCID 700EthanolamineHCID 68983635HCID 68983635、化合物

生成物 1

HCID 57664575HCID 57664575、化合物

実験手順

N-Cyclopropyl-N-{1-[3-(2-hydroxyethylamino)hexanoyl]piperidin-4-yl}-3-trifluoromethylbenzenesulfonamide (40) was prepared by reacting N-cyclopropyl-N-(1-hex-2-enoyl-piperidin-4-yl)-3-trifluoromethyl-benzenesulfonamide (250 mg, 0.56 mmol) and ethanolamine (2 mL) as described in Example 26 above. The reaction mixture was cooled and partitioned between ether (100 mL) and 1M sodium hydroxide solution (100 mL). The organic phase was separated, dried (MgSO4) and the solvent evaporated to dryness in vacuo to leave a colourless gum. The residue was chromatographed over flash silica eluting with ethyl acetate:methanol:ammonia (100:10:1) to give the free base 40 (100 mg). This was converted to the fumarate salt (95 mg, 27%) which was a white solid. LC: 100%. MS: m/z=506.2, 507.3, 508.2 (M+H). 1H NMR (400 MHz, DMSO-d6): (1:1 mixture of rotamers) δ 8.22 (1H, d, J=7.5 Hz), 8.13 (2H, m), 7.92 (1H, t, J=7.5 Hz), 6.47 (1H, s), 4.43 (1H, d, J=13.3 Hz), 4.10 (1H, t, J=13.3 Hz), 3.88 (1H, d, J=13.3 Hz), 3.55 (2H, m), 3.25 (1H, m), 3.05 (1H, t, J=13.3 Hz), 2.85 (2H, m), 2.70-2.50 (3H, m), 1.96 (1H, m), 1.80-1.20 (8H, m), 0.88-0.65 (7H, m).

後処理

  1. customN-Cyclopropyl-N-{1-[3-(2-hydroxyethylamino)hexanoyl]piperidin-4-yl}-3-trifluoromethylbenzenesulfonamide (40) was prepared
  2. temperatureThe reaction mixture was cooled
  3. custompartitioned between ether (100 mL) and 1M sodium hydroxide solution (100 mL)
  4. customThe organic phase was separated
  5. dry with materialdried (MgSO4)
  6. customthe solvent evaporated to dryness in vacuo
  7. customto leave a colourless gum
  8. customThe residue was chromatographed over flash silica eluting with ethyl acetate:methanol:ammonia (100:10:1)

出典と根拠

ORDレコード
ord-a28a32f5bd1e4aa2934856c42fa46bf3
出典データセット
uspto-grants-2015_04
特許番号
US09000174B2

反応ノート

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