Water → (S)-N-(1-azido-3,3-dimethylbutan-2-yl)-2-chloro-5-fluoropyrimidin-4-amine

HRID 1055149Notes

Reaction equation

CS(O[CH2:6][C@@H:7]([NH:12][C:13]1[C:18]([F:19])=[CH:17][N:16]=[C:15]([Cl:20])[N:14]=1)[C:8]([CH3:11])([CH3:10])[CH3:9])(=O)=O.[N-:21]=[N+:22]=[N-:23].[Na+].O>CN(C=O)C>[N:21]([CH2:6][C@@H:7]([NH:12][C:13]1[C:18]([F:19])=[CH:17][N:16]=[C:15]([Cl:20])[N:14]=1)[C:8]([CH3:11])([CH3:10])[CH3:9])=[N+:22]=[N-:23]

Participants

Conditions

Temperature: 70 °C

Procedure

A mixture of (S)-2-((2-chloro-5-fluoropyrimidin-4-yl)amino)-3,3-dimethylbutyl methanesulfonate, 75a, (2.37 g, 7.26 mmol) and sodium azide (1.89 g, 29.07 mmol) in DMF (50 mL) was heated at 70° C. for 6 hours. The reaction mixture was cooled to room temperature and poured into water. The aqueous phase was extracted with EtOAc (2×25 mL), dried (MgSO4), filtered and concentrated in vacuo. The crude product was purified via silica gel chromatography (0-20% EtOAc/Hexanes gradient) to afford 1.2 g of the desired product as a white crystalline solid: 1H NMR (400 MHz, CDCl3) δ 7.86 (dd, J=2.6, 1.1 Hz, 1H), 5.07 (m, 1H), 4.32-4.09 (m, 1H), 3.60 (dd, J=12.8, 3.9 Hz, 1H), 3.34 (dd, J=12.8, 7.6 Hz, 1H), 0.96 (m, 9H); LCMS Gradient 10-90%, 0.1% formic acid, 5 minutes, C18/ACN, Retention Time=3.28 minutes (M+H) 273.14.

Workup

temperatureThe reaction mixture was cooled to room temperature
extractionThe aqueous phase was extracted with EtOAc (2×25 mL)
dry with materialdried (MgSO4)
filtrationfiltered
concentrationconcentrated in vacuo
customThe crude product was purified via silica gel chromatography (0-20% EtOAc/Hexanes gradient)

Sources & evidence

ORD record: ord-503df9249c954e6badd37a64deb8e34b
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09394302B2

Reaction notes

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