Lithium Hydroxide → racemic 3-[[2-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoro-pyrimidin-4-yl]amino]-2-hydroxy-1-methyl-cyclohexanecarboxylic acid

HRID 75028Notes

Reaction equation

HRID 75028 reaction equation
C[O:2][C:3]([C:5]1([CH3:40])[CH2:10][CH2:9][CH2:8][CH:7]([NH:11][C:12]2[C:17]([F:18])=[CH:16][N:15]=[C:14]([C:19]3[C:27]4[C:22](=[N:23][CH:24]=[C:25]([Cl:28])[CH:26]=4)[N:21](S(C4C=CC(C)=CC=4)(=O)=O)[CH:20]=3)[N:13]=2)[CH:6]1[OH:39])=[O:4].C1COCC1.[Li+].[OH-]>CO>[Cl:28][C:25]1[CH:26]=[C:27]2[C:19]([C:14]3[N:13]=[C:12]([NH:11][CH:7]4[CH2:8][CH2:9][CH2:10][C:5]([CH3:40])([C:3]([OH:4])=[O:2])[CH:6]4[OH:39])[C:17]([F:18])=[CH:16][N:15]=3)=[CH:20][NH:21][C:22]2=[N:23][CH:24]=1

Participants

5

Reactant 3

HCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 67285771Racemic methyl-3-[[2-[5-chloro-1-(p-tolylsulfonyl)pyrrolo[2,3-b]pyridin-3-yl]-5-fluoro-pyrimidin-4-yl]amino]-2-hydroxy-1-methyl-cyclohexanecarboxylate2×

Product 1

HCID 67286911racemic 3-[[2-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoro-pyrimidin-4-yl]amino]-2-hydroxy-1-methyl-cyclohexanecarboxylic acid

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Racemic methyl-3-[[2-[5-chloro-1-(p-tolylsulfonyl)pyrrolo[2,3-b]pyridin-3-yl]-5-fluoro-pyrimidin-4-yl]amino]-2-hydroxy-1-methyl-cyclohexanecarboxylate, 66f, (0.100 g, 0.170 mmol) was dissolved in MeOH (1 mL) and THF (1 mL) and treated with aqueous LiOH (0.24 mL of 1 M solution, 0.24 mmol) and the reaction was heated to reflux overnight. The reaction was cooled to room temperature and the resulting material directly purified by preparatory HPLC to afford 20 mg of racemic 3-[[2-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoro-pyrimidin-4-yl]amino]-2-hydroxy-1-methyl-cyclohexanecarboxylic acid. The enantiomers of the racemic material were separated by chiral SFC purification to afford 6 mg of (1R,2R,3R)-3-[[2-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoro-pyrimidin-4-yl]amino]-2-hydroxy-1-methyl-cyclohexanecarboxylic acid and 6 mg of (1S,2S,3S)-3-[[2-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoro-pyrimidin-4-yl]amino]-2-hydroxy-1-methyl-cyclohexanecarboxylic acid. LCMS: 420.36 (M+1).

Workup

  1. temperaturethe reaction was heated
  2. temperatureto reflux overnight
  3. customthe resulting material directly purified by preparatory HPLC

Sources & evidence

ORD record
ord-96fae39709b14ef1a42ca3b252d36801
Source dataset
uspto-grants-2014_09
Patent number
US08829007B2

Reaction notes

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