Carbonate Ion → (2S)-({[8-(cyclohexylmethoxy)-2-methylimidazo[1,2-a]pyridin-3-yl]carbonyl}amino)(phenyl)acetic acid

HRID 64479

Reaction equation

HRID 64479 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.Cl.C[O:24][C:25](=[O:34])[C@H:26]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[NH2:27].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:27][C@@H:26]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)[C:25]([OH:34])=[O:24])=[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 11217910(S)-(+)-2-Phenylglycine methyl ester hydrochlorideHCID 711084908-(Cyclohexylmethoxy)-2-methylimidazo[1,2-a]pyridine-3-carboxylic acid

Product 1

HCID 86713507(2S)-({[8-(cyclohexylmethoxy)-2-methylimidazo[1,2-a]pyridin-3-yl]carbonyl}amino)(phenyl)acetic acidYield 79%

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, 6.1 mg of (S)-(+)-2-phenylglycine methyl ester hydrochloride, 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. Subsequently, 50 mg of macroporous triethylammonium methylpolystyrene carbonate (MP-Carbonate manufactured by Biotage) and 50 mg of polystyrene methyl isocyanate (PS-Isocyanate manufactured by Biotage) were added thereto, 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 THF, 200 μl of methanol, and 50 μl of a 1 M aqueous sodium hydroxide solution, followed by stirring at 50° C. for 20 hours. To the reaction mixture that had been left to be cooled to room temperature were added 0.5 ml of water and 50 μl of 1 M hydrochloric acid, followed by concentration under reduced pressure. The obtained residue was purified by preparative HPLC to obtain 6.7 mg of (2S)-({[8-(cyclohexylmethoxy)-2-methylimidazo[1,2-a]pyridin-3-yl]carbonyl}amino)(phenyl)acetic 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 THF, 200 μl of methanol, and 50 μl of a 1 M aqueous sodium hydroxide solution
  5. stirringby stirring at 50° C. for 20 hours
  6. waitTo the reaction mixture that had been left
  7. temperatureto be cooled to room temperature
  8. additionwere added 0.5 ml of water and 50 μl of 1 M hydrochloric acid
  9. concentrationfollowed by concentration under reduced pressure
  10. customThe obtained residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-571b85d6b1e2493ab33fe1659049a075
Source dataset
uspto-grants-2016_09
Patent number
US09447090B2

Linked notes

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