Diisopropylethylamine → HCID 70816785, 화합물

HRID 1753913노트

반응식

HRID 1753913 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(C(C)C)C(C)C)C.Cl.C(N=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1.[NH2:52][CH2:53][C@@H:54]1[CH2:59][CH2:58][CH2:57][CH2:56][C@H:55]1[OH:60]>ClCCl.C(OCC)(=O)C.[Cl-].[NH4+]>[OH:60][C@@H:55]1[CH2:56][CH2:57][CH2:58][CH2:59][C@H:54]1[CH2:53][NH:52][C:10]([C:9]1[C:4]([CH:1]([CH3:2])[CH3:3])=[N:5][C:6]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)=[CH:7][C:8]=1[CH3:13])=[O:12]

참가 물질

9

반응물 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2724658trans-2-Aminomethyl-1-cyclohexanolHCID 27960291-Hydroxybenzotriazole hydrateHCID 70817044HCID 70817044, 화합물

생성물 1

HCID 70816785HCID 70816785, 화합물수율 63%

시약·촉매·용매 3

HCID 6344Dichloromethane용매HCID 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) (0.20 g, 0.76 mmol) in dichloromethane (15 ml) are added N-ethyl-diisopropylamine (0.32 ml, 0.89 mmol), 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (0.17 g, 0.91 mmol), and 1-hydroxybenzotriazole hydrate (0.02 g, 0.15 mmol). The mixture is stirred for 15 min at RT, and then cooled to 0° C., before (1R,2S)-2-(aminomethyl)cyclohexanol (0.09 g, 0.76 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 N-[[(1S,2R)-2-hydroxy-cyclohexyl]-methyl]-2-isopropyl-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid amide (example X7) (0.18 g, 0.48 mmol, 63%). [M+H]+376.3.

후처리

  1. additionis added
  2. stirringstirring
  3. waitis continued for 18 h
  4. customAfter completion of the reaction
  5. customThe organic layer is separated
  6. washwashed with saturated sodium hydrogencarbonate solution and brine
  7. dry with materialdried over magnesium sulphate
  8. customevaporated to dryness
  9. customThe crude product is purified by flash chromatography (silica gel, 50% ethyl acetate/cyclohexane)

출처 및 근거

ORD 기록
ord-eabe245b6376419ebe490432d8fc37e4
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09168259B2

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