1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 70816915、化合物

HRID 1753908ノート

反応式

HRID 1753908 の反応式
[CH:1]1([C:4]2[C:9]([C:10]([OH:12])=O)=[C:8]([CH3:13])[CH:7]=[C:6]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[N:5]=2)[CH2:3][CH2:2]1.C(N(C(C)C)C(C)C)C.C(N=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1.[NH2:51][CH2:52][C@@H:53]1[CH2:58][CH2:57][CH2:56][CH2:55][C@H:54]1[OH:59]>ClCCl.C(OCC)(=O)C.[Cl-].[NH4+]>[CH:1]1([C:4]2[C:9]([C:10]([NH:51][CH2:52][C@@H:53]3[CH2:58][CH2:57][CH2:56][CH2:55][C@H:54]3[OH:59])=[O:12])=[C:8]([CH3:13])[CH:7]=[C:6]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[N:5]=2)[CH2:2][CH2:3]1

参加物

9

反応物 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 2724658trans-2-Aminomethyl-1-cyclohexanolHCID 27960291-Hydroxybenzotriazole hydrateHCID 672877532-Cyclopropyl-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid

生成物 1

HCID 70816915HCID 70816915、化合物収率 98%

試薬・触媒・溶媒 3

HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒HCID 25517Ammonium Chloride溶媒

実験手順

To a solution of 2-cyclopropyl-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid (synthesized according to the methods described in sections a) to d) of example X1) (0.15 g, 0.57 mmol) in dichloromethane (10 ml) are added N-ethyl-diisopropylamine (0.24 ml, 1.43 mmol), 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (0.13 g, 0.69 mmol), and 1-hydroxybenzotriazole hydrate (0.015 g, 0.11 mmol). The mixture is stirred for 15 min at RT, and then cooled to 0° C., before (1R,2S)-2-(aminomethyl)cyclohexanol (0.07 g, 0.57 mmol) is added and stirring is continued for 3 days. 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, 30% ethyl acetate/cyclohexane) to yield 2-cyclopropyl-N-[[(1S,2R)-2-hydroxy-cyclohexyl]-methyl]-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid amide (example X2) (0.21 g, 0.56 mmol, 98%). [M+H]+374.2.

後処理

  1. additionis added
  2. stirringstirring
  3. waitis continued for 3 days
  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, 30% ethyl acetate/cyclohexane)

出典と根拠

ORDレコード
ord-580441f2c4654eb9b7eb62aaf2358d9d
出典データセット
uspto-grants-2015_10
特許番号
US09168259B2

反応ノート

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