Water → HCID 86714765, compound

HRID 1055093Notes

Reaction equation

[Cl-].[CH3:2][O:3][C:4](=[O:13])[CH2:5][CH:6]([C:8]1([CH3:12])[CH2:11][CH2:10][CH2:9]1)[NH3+:7].[Cl:14][C:15]1[N:20]=[C:19](Cl)[C:18]([F:22])=[CH:17][N:16]=1.C(N(CC)CC)C.O>C1COCC1.CCO.ClCCl>[Cl:14][C:15]1[N:20]=[C:19]([NH:7][CH:6]([C:8]2([CH3:12])[CH2:11][CH2:10][CH2:9]2)[CH2:5][C:4]([O:3][CH3:2])=[O:13])[C:18]([F:22])=[CH:17][N:16]=1

Participants

Conditions

Temperature: 55 °C

Procedure

Racemic 3-methoxy-1-(1-methylcyclobutyl)-3-oxopropan-1-aminium chloride, 117a, (3.3 g, 15.9 mmol) was dissolved in a mixture of 59 mL THF and 6.6 mL EtOH and the solution was cooled in an ice bath. 2,4-Dichloro-5-fluoro-pyrimidine (2.9 g, 18.0 mmol) was added followed by dropwise addition of triethylamine (5.1 g, 51.0 mmol). The reaction mixture was stirred at 55° C. for 17 hours. The reaction mixture was cooled to room temperature after which water and dichloromethane were added. The phases were separated and the aqueous layer was washed with dichloromethane. The organic layers were combined and washed with brine. The solvents were removed and the residue was purified via silica gel chromatography (EtOAc/Hexanes) to afford the desired product: LCMS Gradient 10-90%, 0.1% formic acid, 5 minutes, C18/ACN, RT=3.23 minutes (M+H) 302.35.

Workup

temperaturethe solution was cooled in an ice bath
additionwere added
customThe phases were separated
washthe aqueous layer was washed with dichloromethane
washwashed with brine
customThe solvents were removed
customthe residue was purified via silica gel chromatography (EtOAc/Hexanes)

Sources & evidence

ORD record: ord-a73ffa495570416994f4eed4a9b720e7
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09394302B2

Reaction notes

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