Triethylamine → 2-Isopropyl-4-methyl-6-morpholin-4-yl-N-(4,4,4-trifluoro-3-hydroxy-butyl)-pyridine-3-carboxylic acid amide

HRID 1753912노트

반응식

HRID 1753912 반응식
[CH:1]([C:4]1[C:9]([C:10]([OH:12])=O)=[C:8]([CH3:13])[CH:7]=[C:6]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[N:5]=1)([CH3:3])[CH3:2].C(N(CC)CC)C.Cl.[NH2:28][CH2:29][CH2:30][CH:31]([OH:36])[C:32]([F:35])([F:34])[F:33]>O1CCCC1.C(OCC)(=O)C.[Cl-].[NH4+]>[CH:1]([C:4]1[C:9]([C:10]([NH:28][CH2:29][CH2:30][CH:31]([OH:36])[C:32]([F:35])([F:34])[F:33])=[O:12])=[C:8]([CH3:13])[CH:7]=[C:6]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[N:5]=1)([CH3:2])[CH3:3]

참가 물질

7

반응물 3

HCID 8471TriethylamineHCID 545928324-Amino-1,1,1-trifluorobutan-2-ol hydrochlorideHCID 708170442-Isopropyl-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid

생성물 1

HCID 708168272-Isopropyl-4-methyl-6-morpholin-4-yl-N-(4,4,4-trifluoro-3-hydroxy-butyl)-pyridine-3-carboxylic acid amide수율 60%

시약·촉매·용매 3

HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매HCID 25517Ammonium Chloride용매

실험 절차

To a solution of 2-isopropyl-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid (synthesized similar to the methods described in sections a) to d) of example X1) (1.40 g, 5.30 mmol) in tetrahydrofuran (40 ml) are added triethylamine (2.9 ml, 21.2 mol) and 0-(7-azabenzotriazol-1-yl)N,N,N′,N′-tetramethyluronium hexafluorophosphate (2.9 g, 5.3 mmol). The mixture is stirred for 15 min at RT, before 4-amino-1,1,1-trifluorobutan-2-ol hydrochloride (1.05 g, 5.8 mmol) is added and stirring is continued for 18 h. After completion of the reaction, the mixture is diluted with ethyl acetate and 10% aqueous ammonium chloride. The organic layer is separated and washed with saturated sodium hydrogencarbonate solution and brine, dried over magnesium sulphate and evaporated to dryness. The crude product is purified by flash chromatography (silica gel, 50% ethyl acetate/cyclohexane) to yield 2-Isopropyl-4-methyl-6-morpholin-4-yl-N-(4,4,4-trifluoro-3-hydroxy-butyl)-pyridine-3-carboxylic acid amide (example X6) (1.24 g, 3.18 mmol, 60%). [M+H]+390.2.

후처리

  1. additionis added
  2. customAfter completion of the reaction
  3. customThe organic layer is separated
  4. washwashed with saturated sodium hydrogencarbonate solution and brine
  5. dry with materialdried over magnesium sulphate
  6. customevaporated to dryness
  7. customThe crude product is purified by flash chromatography (silica gel, 50% ethyl acetate/cyclohexane)

출처 및 근거

ORD 기록
ord-3f01316169d04c97bc0891c184758b1c
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09168259B2

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