Trifluoroacetic acid → HCID 67403905、化合物

HRID 914034ノート

反応式

HRID 914034 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([CH:11]([O:16][CH2:17][C:18]3([C:31]4[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=4)[CH2:23][CH2:22][N:21]([C:24](OC(C)(C)C)=O)[CH2:20][CH2:19]3)[C:12]([O:14][CH3:15])=[O:13])[CH:10]=1)[NH:7][N:6]=[CH:5]2.[F:38][C:39]([F:44])([F:43])[C:40]([OH:42])=[O:41]>>[F:38][C:39]([F:44])([F:43])[C:40]([OH:42])=[O:41].[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([CH:11]([O:16][CH2:17][C:18]3([C:31]4[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=4)[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]3)[C:12]([O:14][CH3:15])=[O:13])[CH:10]=1)[NH:7][N:6]=[CH:5]2

参加物

3

反応物 2

HCID 6422Trifluoroacetic acidHCID 57546152HCID 57546152、化合物

生成物 1

HCID 67403905HCID 67403905、化合物

実験手順

tert-butyl 4-((1-(5-chloro-1H-indazol-7-yl)-2-methoxy-2-oxoethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate (20 mg) was dissolved in trifluoroacetic acid (20% in dichloromethane, 1.5 mL) and stirred for 20 min at room temperature. The reaction was concentrated and the resulting residues loaded onto a strong cation exchange cartridge. The cartridge was flushed with several volumes of methanol which were discarded. The amine was eluted with 2M ammonia in methanol and concentrated. The unprotected piperidine was dissolved in acetonitrile (1 mL) and treated with formalin (50 μL) and sodium cyanoborohydride (2.4 mg) and one drop of acetic acid. The reaction was stirred at room temperature for 1 h. The reaction was concentrated. The resulting residue was dissolved in trifluoroacetic acid (25% in dichloromethane, 2 mL), stirred for 5 min, and concentrated. The resulting residue was purified by preparative HPLC to afford the title compound. 1H-NMR (CD3OD, 500 MHz) δ 8.05 (m, 1H), 7.78 (m, 1H), 7.44 (m, 2H), 7.22 (m, 0.75H), 7.13 (m, 1.8H), 7.03 (m, 0.6H), 5.34 (s, 0.3H), 5.27 (s, 0.7H), 3.69 (m, 4H), 3.47 (m, 4H), 2.55-3.00 (m, 7H), 2.00-2.55 (m, 2.5H). Mass spec.: 446.24 (MH)+.

後処理

  1. concentrationThe reaction was concentrated
  2. customThe cartridge was flushed with several volumes of methanol which
  3. washThe amine was eluted with 2M ammonia in methanol
  4. concentrationconcentrated
  5. dissolutionThe unprotected piperidine was dissolved in acetonitrile (1 mL)
  6. additiontreated with formalin (50 μL) and sodium cyanoborohydride (2.4 mg) and one drop of acetic acid
  7. stirringThe reaction was stirred at room temperature for 1 h
  8. concentrationThe reaction was concentrated
  9. dissolutionThe resulting residue was dissolved in trifluoroacetic acid (25% in dichloromethane, 2 mL)
  10. stirringstirred for 5 min
  11. concentrationconcentrated
  12. customThe resulting residue was purified by preparative HPLC

出典と根拠

ORDレコード
ord-46ef785cb95f4a59bdc7e27faa7217bc
出典データセット
uspto-grants-2011_09
特許番号
US08026257B2

反応ノート

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