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

HRID 64480

Reaction equation

HRID 64480 reaction equation
[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

Participants

10

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-b46f4765712a44e6b6fb757755d6f3e4
Source dataset
uspto-grants-2016_09
Patent number
US09447090B2

Linked notes

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