Sodium methanolate methanol → (S)-tetrahydrofuran-3-yl 3-(2-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoropyrimidin-4-ylamino)azetidine-1-carboxylate

HRID 526891Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[N:16]=[C:15]([NH:17][CH:18]4[CH2:21][N:20]([C:22]([O:24][C@H:25]5[CH2:29][CH2:28][O:27][CH2:26]5)=[O:23])[CH2:19]4)[C:14]([F:30])=[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.C[O-].[Na+].CO>CO>[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[N:16]=[C:15]([NH:17][CH:18]4[CH2:19][N:20]([C:22]([O:24][C@H:25]5[CH2:29][CH2:28][O:27][CH2:26]5)=[O:23])[CH2:21]4)[C:14]([F:30])=[CH:13][N:12]=3)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1

Participants

Conditions

Temperature: 60 °C

Procedure

(S)-tetrahydrofuran-3-yl 3-(2-(5-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoropyrimidin-4-ylamino)azetidine-1-carboxylate, 6d, was dissolved in methanol (2 mL) and then treated with of 25% sodium methoxide/methanol (0.5 mL) and heated at 60° C. in sealed tube. LCMS showed complete reaction after 10 minutes. The resulting solution was quenched with aqueous saturated NH4Cl solution (0.5 mL) then evaporated to dryness and the residue dissolved in DMSO and purified by reverse phase HPLC (ammonium formate buffer) to afford 25.9 mg (55% yield) of the desired product, 422, as a solid.

Workup

customreaction after 10 minutes
customThe resulting solution was quenched with aqueous saturated NH4Cl solution (0.5 mL)
customthen evaporated to dryness
dissolutionthe residue dissolved in DMSO
custompurified by reverse phase HPLC (ammonium formate buffer)

Sources & evidence

ORD record: ord-3dc9bcaf090543bc9c50cf17c5763dac
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09345708B2

Reaction notes

Loading…