(3S,4S)-4-[(S)-3-(4-Fluoro-benzyl)-piperidin-1-ylmethyl]-tetrahydro-pyran-3-ylamine → HCID 44445842, compound

HRID 1169243Notes

Reaction equation

HRID 1169243 reaction equation
[F:1][C:2]1[CH:22]=[CH:21][C:5]([CH2:6][C@@H:7]2[CH2:12][CH2:11][CH2:10][N:9]([CH2:13][C@@H:14]3[CH2:19][CH2:18][O:17][CH2:16][C@H:15]3[NH2:20])[CH2:8]2)=[CH:4][CH:3]=1.C1([O:29][C:30](=O)[NH:31][C:32]2[S:33][C:34]([C:38](=[O:40])[CH3:39])=[C:35]([CH3:37])[N:36]=2)C=CC=CC=1>C(#N)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][C@@H:7]2[CH2:12][CH2:11][CH2:10][N:9]([CH2:13][C@@H:14]3[CH2:19][CH2:18][O:17][CH2:16][C@H:15]3[NH:20][C:30]([NH:31][C:32]3[S:33][C:34]([C:38](=[O:40])[CH3:39])=[C:35]([CH3:37])[N:36]=3)=[O:29])[CH2:8]2)=[CH:21][CH:22]=1

Participants

4

Reactant 2

HCID 21362442(3S,4S)-4-[(S)-3-(4-Fluoro-benzyl)-piperidin-1-ylmethyl]-tetrahydro-pyran-3-ylamineHCID 22259036Phenyl (5-acetyl-4-methyl-1,3-thiazol-2-yl)carbamate

Product 1

HCID 44445842HCID 44445842, compoundYield 23%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

(3S,4S)-4-[(S)-3-(4-Fluoro-benzyl)-piperidin-1-ylmethyl]-tetrahydro-pyran-3-ylamine (49 mg, 160 μmol) and (5-acetyl-4-methylthiazol-2-yl)-carbamic acid phenyl ester (49 mg, 176 μmol) were dissolved in acetonitrile (1 mL) and the mixture was stirred at room temperature. After 24 h , the mixture was concentrated, dissolved in ethyl acetate, washed with water, dried (Na2SO4) and concentrated. The residue was purified by reverse phase high pressure liquid chromatography (C18, 10-100% acetonitrile in water, containing 0.05% trifluoroacetic acid), then by flash column chromatography (5% methanol in dichloromethane, containing 0.5% ammonium hydroxide) to provide the product as a glass (18 mg, 23%). 1H NMR (300 mHz, CD3OD) δ7.05 (m, 2H), 6.87 (m, 2H), 3.90 (dd, J=11.0, 4.4 Hz, 1H), 3.84 (m, 1H), 3.53 (td, J=9.5, 4.3 Hz, 1H), 3.40 (bt, 1H), 3.10 (m, 1H), 2.90 (bd, 1H), 2.75 (bd, 1H), 2.58 (s, 3H), 2.48 (s, 3H), 2.45 (m, 3H), 2.21 (dd, J=13.6, 6.3 Hz, 1H), 1.91 (bt, 1H), 1.8-1.5 (7H), 1.37 (m, 1H), 0.92 (m, 1H), ESI MS: (M+H)+=489.4 (100%).

Workup

  1. concentrationthe mixture was concentrated
  2. dissolutiondissolved in ethyl acetate
  3. washwashed with water
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. customThe residue was purified by reverse phase high pressure liquid chromatography (C18, 10-100% acetonitrile in water, containing 0.05% trifluoroacetic acid)
  7. additionby flash column chromatography (5% methanol in dichloromethane, containing 0.5% ammonium hydroxide)

Sources & evidence

ORD record
ord-1d2e6fee6c3f4527be83ea545b7f9e08
Source dataset
uspto-grants-2003_09
Patent number
US06627629B2

Reaction notes

Loading…