2-(Oxan-4-yl)ethan-1-amine → Ondelopran

HRID 228458ノート

反応式

HRID 228458 の反応式
[F:1][C:2]1[CH:17]=[C:16]([CH:18]=O)[CH:15]=[CH:14][C:3]=1[O:4][C:5]1[CH:13]=[CH:12][C:8]([C:9]([NH2:11])=[O:10])=[CH:7][N:6]=1.[O:20]1[CH2:25][CH2:24][CH:23]([CH2:26][CH2:27][NH2:28])[CH2:22][CH2:21]1.[BH4-].[Na+]>CO>[F:1][C:2]1[CH:17]=[C:16]([CH2:18][NH:28][CH2:27][CH2:26][CH:23]2[CH2:24][CH2:25][O:20][CH2:21][CH2:22]2)[CH:15]=[CH:14][C:3]=1[O:4][C:5]1[CH:13]=[CH:12][C:8]([C:9]([NH2:11])=[O:10])=[CH:7][N:6]=1

参加物

5

反応物 3

HCID 27731982-(Oxan-4-yl)ethan-1-amineHCID 4311764Sodium borohydrideHCID 59730086HCID 59730086、化合物

生成物 1

HCID 10457387Ondelopran

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

実験手順

Place 6-(2-fluoro-4-formylphenoxy)nicotinamide (Example 223, step 1) (0.700 g, 2.69 mmol), 2-(tetrahydropyran-4-yl)ethylamine (0.348 g, 2.69 mmol) and 3 Å molecular sieves in a vial. Add methanol (13.5 mL), cap and stir overnight. Add NaBH4 (0.204 g, 5.38 mmol) and stir until the gasses stop evolving. Filter the reaction mixture, then concentrate it. Purify by chromatography eluting with 0% to 20% (2.0 M NH3 in methanol) in ethyl acetate over 1 hour at 20 mL/min to give 6-(2-fluoro-4-{[2-(tetrahydropyran-4-yl)ethylamino]methyl}phenoxy)nicotinamide. (0.717 g, 71.3%). Dissolve the compound in dichloromethane:methanol (10 mL) and add 1 equivalent of 0.50 M methanesulfonic acid in dichloromethane. Stir the solution for a short time before concentrating to give the title compound (0.904 g): TOF MS ES+ 374.2 (M+H)+, HRMS calcd for C20H25N3O3F 374.1880 (M+H)+, found 374.1881, time 0.55 min; HPLC [YMC-Pro pack C-18 (150×4.6 mm, S-5 microm), 0.05% TFA/acetonitrile in 0.05% TFA/water at 1.0 mL/min, 10-20% over 5 min, 20-95% over 18], tR=8.7 min, 100% purity.

後処理

  1. filtrationFilter the reaction mixture
  2. concentrationconcentrate it
  3. customPurify by chromatography
  4. washeluting with 0% to 20% (2.0 M NH3 in methanol) in ethyl acetate over 1 hour at 20 mL/min

出典と根拠

ORDレコード
ord-7e1fda8c852446668ef8d0b47bd88a39
出典データセット
uspto-grants-2009_07
特許番号
US07560463B2

反応ノート

読み込み中…