Lithium Hydroxide → 6-[[5-fluoro-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl]amino]norbornane-2-carboxylic acid

HRID 75049Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[N:16]=[C:15](S(C)=O)[C:14]([F:20])=[CH:13][N:12]=3)=[CH:9][N:8](S(C3C=CC(C)=CC=3)(=O)=O)[C:5]2=[N:6][CH:7]=1.[NH2:31][CH:32]1[CH:37]2[CH2:38][CH:34]([CH2:35][CH:36]2[C:39]([OH:41])=[O:40])[CH2:33]1.C(N(C(C)C)CC)(C)C.[Li+].[OH-].FC(F)(F)C(O)=O>C1COCC1.CO>[F:20][C:14]1[C:15]([NH:31][CH:32]2[CH:37]3[CH2:38][CH:34]([CH2:35][CH:36]3[C:39]([OH:41])=[O:40])[CH2:33]2)=[N:16][C:11]([C:10]2[C:4]3[C:5](=[N:6][CH:7]=[C:2]([F:1])[CH:3]=3)[NH:8][CH:9]=2)=[N:12][CH:13]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 5-fluoro-3-(5-fluoro-4-methylsulfinyl-pyrimidin-2-yl)-1-(p-tolylsulfonyl)pyrrolo[2,3-b]pyridine (0.187 g, 0.417 mmol) and 6-aminobicyclo-[2.2.1]heptane-2-carboxylic acid, 72h, (0.080 g, 0.417 mmol) in THF (3 mL) was added diisopropylethylamine (0.291 mL, 1.670 mmol). The reaction mixture was heated at 80° C. overnight. Aqueous LiOH (3 mL of 2M solution, 6.000 mmol) was added and the mixture was heated for another 7 hours. The mixture was diluted with MeOH, neutralized with trifluoroacetic acid, filtered and the resulting filtrate was purified by preparatory HPLC chromatography to afford 50 mg of desired product.

Workup

temperaturethe mixture was heated for another 7 hours
filtrationfiltered
customthe resulting filtrate was purified by preparatory HPLC chromatography

Sources & evidence

ORD record: ord-086f6eb3d4f94ecb9d6ad9979dc47cb4
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08829007B2

Reaction notes

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