Lithium Hydroxide → (S)-2-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoro-N-(1-(2,2,2-trifluoroethyl)piperidin-3-yl)pyrimidin-4-amine

HRID 526877Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[N:16]=[C:15]([NH:17][C@H:18]4[CH2:23][CH2:22][CH2:21][N:20]([CH2:24][C:25]([F:28])([F:27])[F:26])[CH2:19]4)[C:14]([F:29])=[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.[Li+].[OH-]>C1COCC1.[Cl-].[Na+].O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[N:16]=[C:15]([NH:17][C@H:18]4[CH2:23][CH2:22][CH2:21][N:20]([CH2:24][C:25]([F:28])([F:26])[F:27])[CH2:19]4)[C:14]([F:29])=[CH:13][N:12]=3)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1

Participants

Conditions

Temperature: 120 °C

Procedure

To a solution of 2-[5-chloro-1-(p-tolylsulfonyl)pyrrolo[2,3-b]pyridin-3-yl]-5-fluoro-N-[(3S)-1-(2,2,2-trifluoroethyl)-3-piperidyl]pyrimidin-4-amine, 3a, (0.10 g, 0.18 mmol) in THF was added 1M LiOH (0.90 mL, 0.90 mmol) solution. The reaction mixture was heated in microwave at 120° C. for 10 minutes. The reaction mixture was diluted with brine, extracted with EtOAc, then with 20% isopropanol/CH2Cl2. The combined organic phases were dried (MgSO4), filtered and concentrated in vacuo. The resulting residue was purified via silica gel chromatography (0-10% MeOH:CH2Cl2) to afford the desired product, 1339, as a white solid.

Workup

extractionextracted with EtOAc
dry with materialThe combined organic phases were dried (MgSO4)
filtrationfiltered
concentrationconcentrated in vacuo
customThe resulting residue was purified via silica gel chromatography (0-10% MeOH:CH2Cl2)

Sources & evidence

ORD record: ord-328d3413979f404ea3f492524fe6a69e
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09345708B2

Reaction notes

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