Carbonate Ion → (3R)-3-({[8-(cyclohexylmethoxy)-2-methylimidazo[1,2-a]pyridin-3-yl]carbonyl}amino)-4-phenylbutanoic acid

HRID 64480

반응식

HRID 64480 반응식
[CH:1]1([CH2:7][O:8][C:9]2[C:10]3[N:11]([C:15]([C:19]([OH:21])=O)=[C:16]([CH3:18])[N:17]=3)[CH:12]=[CH:13][CH:14]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:22][C@H:23]([CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[CH2:24][C:25]([O:27]C(C)(C)C)=[O:26].ON1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.N=C=N.C([NH+](CC)CC)C.C(=O)([O-])[O-].[N-]=C=O>CN(C=O)C>[CH:1]1([CH2:7][O:8][C:9]2[C:10]3[N:11]([C:15]([C:19]([NH:22][C@H:23]([CH2:32][C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)[CH2:24][C:25]([OH:27])=[O:26])=[O:21])=[C:16]([CH3:18])[N:17]=3)[CH:12]=[CH:13][CH:14]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

참가 물질

10

반응물 8

HCID 19660Carbonate IonHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 105034IsocyanateHCID 160435CarbodiimideHCID 1385867TriethylammoniumHCID 1501867(R)-tert-Butyl 3-amino-4-phenylbutanoateHCID 711084908-(Cyclohexylmethoxy)-2-methylimidazo[1,2-a]pyridine-3-carboxylic acid

생성물 1

HCID 86713508(3R)-3-({[8-(cyclohexylmethoxy)-2-methylimidazo[1,2-a]pyridin-3-yl]carbonyl}amino)-4-phenylbutanoic acid수율 61.9%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a mixture of 5.8 mg of 8-(cyclohexylmethoxy)-2-methylimidazo[1,2-a]pyridine-3-carboxylic acid, 7.1 mg of tert-butyl (3R)-3-amino-4-phenylbutanoate, 2.7 mg of 1-hydroxybenzotriazole, 700 μl of DMF, and 19 μl of diisopropylethylamine was added 50 mg of polystyrene N-cyclohexylcarbodiimide-N′-propyloxymethyl (PS-Carbodiimide manufactured by Biotage), followed by stirring at room temperature for 20 hours. To the reaction mixture were added 50 mg of macroporous triethylammonium methylpolystyrene carbonate (MP-Carbonate manufactured by Biotage) and 50 mg of polystyrene methyl isocyanate (PS-Isocyanate manufactured by Biotage), followed by stirring at room temperature for 2 hours. The resin was removed by filtration, the filtrate was concentrated under reduced pressure, and to the obtained residue were added 100 μl of 1,4-dioxane and 200 μl of a 4 M hydrogen chloride/1,4-dioxane solution, followed by stirring at room temperature for 20 hours. The reaction mixture was concentrated under reduced pressure and the obtained residue was purified by preparative HPLC to obtain 5.6 mg of (3R)-3-({[8-(cyclohexylmethoxy)-2-methylimidazo[1,2-a]pyridin-3-yl]carbonyl}amino)-4-phenylbutanoic acid.

후처리

  1. stirringby stirring at room temperature for 2 hours
  2. customThe resin was removed by filtration
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. additionto the obtained residue were added 100 μl of 1,4-dioxane and 200 μl of a 4 M hydrogen chloride/1,4-dioxane solution
  5. stirringby stirring at room temperature for 20 hours
  6. concentrationThe reaction mixture was concentrated under reduced pressure
  7. customthe obtained residue was purified by preparative HPLC

출처 및 근거

ORD 기록
ord-b46f4765712a44e6b6fb757755d6f3e4
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09447090B2

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