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

HRID 131003노트

반응식

HRID 131003 반응식
[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

참가 물질

5

반응물 3

HCID 27731982-(Oxan-4-yl)ethan-1-amineHCID 4311764Sodium borohydrideHCID 59730086HCID 59730086, 화합물

생성물 1

HCID 10457387Ondelopran

시약·촉매·용매 1

HCID 887Methanol용매

실험 절차

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 {acute over (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.

후처리

  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

출처 및 근거

ORD 기록
ord-42fd9502584b4e0381bc8a9bf67a48a5
출처 데이터셋
uspto-grants-2008_06
특허 번호
US07381719B2

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