Chloroform → Avatrombopag Impurity 22

HRID 1869582Notes

Reaction equation

HRID 1869582 reaction equation
[Cl:1][C:2]1[C:3](Cl)=[N:4][CH:5]=[C:6]([CH:33]=1)[C:7]([NH:9][C:10]1[S:11][C:12]([N:21]2[CH2:26][CH2:25][N:24]([CH:27]3[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]3)[CH2:23][CH2:22]2)=[C:13]([C:15]2[S:16][CH:17]=[C:18]([Cl:20])[CH:19]=2)[N:14]=1)=[O:8].C(Cl)(Cl)Cl.[NH:39]1[CH2:49][CH2:48][CH:42]([C:43]([O:45][CH2:46][CH3:47])=[O:44])[CH2:41][CH2:40]1>C1COCC1>[CH2:46]([O:45][C:43]([CH:42]1[CH2:48][CH2:49][N:39]([C:3]2[C:2]([Cl:1])=[CH:33][C:6]([C:7](=[O:8])[NH:9][C:10]3[S:11][C:12]([N:21]4[CH2:26][CH2:25][N:24]([CH:27]5[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]5)[CH2:23][CH2:22]4)=[C:13]([C:15]4[S:16][CH:17]=[C:18]([Cl:20])[CH:19]=4)[N:14]=3)=[CH:5][N:4]=2)[CH2:40][CH2:41]1)=[O:44])[CH3:47]

Participants

5

Reactant 3

HCID 6212ChloroformHCID 70770Ethyl 4-piperidinecarboxylateHCID 23030584HCID 23030584, compound

Product 1

HCID 87436416Avatrombopag Impurity 22

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 750 mg of the compound of Example 5 in 10 ml of THF, 2.1 ml of ethyl isonipecotate was added at room temperature, the temperature was elevated to 50° C., and the mixture was stirred for 5 hours. To the reaction solution, chloroform was added, and the organic layer was washed with saturated aqueous NaHCO3 and brine and dried over sodium sulfate. After the evaporation of the solvent under reduced pressure, the obtained residue was purified by silica gel column chromatography (chloroform-MeOH=200:1˜100:1) to obtain 881 mg of 1-(3-chloro-5-{[4-(4-chlorothiophen-2-yl)-5-(4-cyclohexylpiperazin-1-yl)thiazol-2-yl]carbamoyl}-2-pyridyl)piperidine-4-carboxylic acid ethyl ester.

Workup

  1. customwas elevated to 50° C.
  2. washthe organic layer was washed with saturated aqueous NaHCO3 and brine
  3. dry with materialdried over sodium sulfate
  4. customAfter the evaporation of the solvent under reduced pressure
  5. customthe obtained residue was purified by silica gel column chromatography (chloroform-MeOH=200:1˜100:1)

Sources & evidence

ORD record
ord-308f61a1266c442b8cea2c100d0279f6
Source dataset
uspto-grants-2009_12
Patent number
US07638536B2

Reaction notes

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