2-(Oxan-4-yl)ethan-1-amine → 6-(2-Methoxy-4-{[2-(tetrahydropyran-4-yl)ethylamino]methyl}phenoxy)pyridazine-3-carboxamide

HRID 130980노트

반응식

HRID 130980 반응식
[CH:1]([C:3]1[CH:18]=[CH:17][C:6]([O:7][C:8]2[N:13]=[N:12][C:11]([C:14]([NH2:16])=[O:15])=[CH:10][CH:9]=2)=[C:5]([O:19][CH3:20])[CH:4]=1)=O.[O:21]1[CH2:26][CH2:25][CH:24]([CH2:27][CH2:28][NH2:29])[CH2:23][CH2:22]1.[BH4-].[Na+]>CO>[CH3:20][O:19][C:5]1[CH:4]=[C:3]([CH2:1][NH:29][CH2:28][CH2:27][CH:24]2[CH2:25][CH2:26][O:21][CH2:22][CH2:23]2)[CH:18]=[CH:17][C:6]=1[O:7][C:8]1[N:13]=[N:12][C:11]([C:14]([NH2:16])=[O:15])=[CH:10][CH:9]=1

참가 물질

5

반응물 3

HCID 27731982-(Oxan-4-yl)ethan-1-amineHCID 4311764Sodium borohydrideHCID 597300016-(4-Formyl-2-methoxyphenoxy)pyridazine-3-carboxamide

생성물 1

HCID 597300186-(2-Methoxy-4-{[2-(tetrahydropyran-4-yl)ethylamino]methyl}phenoxy)pyridazine-3-carboxamide수율 54.4%

시약·촉매·용매 1

HCID 887Methanol용매

실험 절차

Place 6-(4-formyl-2-methoxyphenoxy)pyridazine-3-carboxamide (Example 721, Part C) (0.200 g, 0.732 mmol), 2-(tetrahydropyran-4-yl)ethylamine (0.0993 g, 0.769 mmol) and 3 {acute over (Å)} molecular sieves in a vial. Add methanol (3.6 mL), cap and stir overnight. Add NaBH4 (ca. 3-5 eq in two portions) and stir until the gasses stop evolving. Load the reaction mixture directly onto a 25 g ISCO® pre-load column. Dry the column in a vacuum oven at room temperature. Purify by eluting through a 40 g ISCO® column with 10% to 20% (2.0 M NH3 in methanol) in ethyl acetate. Concentrate the fractions containing the product. Take the solid up in ethyl acetate (50 mL) and wash with 1.0 N NaOH (2×10 mL). Dry the organic layer over Na2SO4, filter and concentrate to give the title compound (0.154 g, 54%): TOF MS ES+ 387.2 (M+H)+, HRMS calcd for C20H27N4O4 387.2032 (M+H)+, found 387.2024, time 0.52 min; Anal. Calcd for C20H26N4O4: C, 62.16; H, 6.78; N, 14.50. Found: C, 61.58; H, 6.66; N, 14.13.

후처리

  1. customDry the column in a vacuum oven at room temperature
  2. customPurify
  3. washby eluting through a 40 g ISCO® column with 10% to 20% (2.0 M NH3 in methanol) in ethyl acetate
  4. concentrationConcentrate the fractions
  5. additioncontaining the product
  6. washwash with 1.0 N NaOH (2×10 mL)
  7. dry with materialDry the organic layer over Na2SO4
  8. filtrationfilter
  9. concentrationconcentrate

출처 및 근거

ORD 기록
ord-cbfcd1f01509499ab3772771b26a6f5e
출처 데이터셋
uspto-grants-2008_06
특허 번호
US07381719B2

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