Ethanolamine → HCID 57664575, compound

HRID 1467897Notes

Reaction equation

HRID 1467897 reaction equation
[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

Participants

3

Reactant 2

HCID 700EthanolamineHCID 68983635HCID 68983635, compound

Product 1

HCID 57664575HCID 57664575, compound

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-a28a32f5bd1e4aa2934856c42fa46bf3
Source dataset
uspto-grants-2015_04
Patent number
US09000174B2

Reaction notes

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