Ammonium Acetate → 1-{5-Chloro-8-[(3S)-3-fluoropyrrolidin-1-yl]quinolin-7-yl}ethanamine

HRID 1192597Notes

Reaction equation

[Cl:1][C:2]1[CH:11]=[C:10]([C:12](=O)[CH3:13])[C:9]([N:15]2[CH2:19][CH2:18][C@H:17]([F:20])[CH2:16]2)=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2.C([O-])(=O)C.[NH4+].C([BH3-])#[N:27].[Na+]>CO.C(#N)C>[Cl:1][C:2]1[CH:11]=[C:10]([CH:12]([NH2:27])[CH3:13])[C:9]([N:15]2[CH2:19][CH2:18][C@H:17]([F:20])[CH2:16]2)=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2

Participants

Conditions

Temperature: 65 °C

Procedure

A mixture of 1-{5-chloro-8-[(3S)-3-fluoropyrrolidin-l-yl]quinolin-7-yl}ethanone (0.10 g, 0.34 mmol) and ammonium acetate (0.263 g, 3.42 mmol) in methanol (1.5 mL) and acetonitrile (1.5 mL) was heated at 65° C. in a sealed tube for 1 hour. After cooling to room temperature, sodium cyanoborohydride (0.064 g, 1.0 mmol). The reaction was heated at 65° C. overnight, cooled to room temperature and quenched with sat. NaHCO3 solution and extracted with Ethyl acetate. The combined organic layers were dried over MgSO4, concentrated and purified on a preparative LCMS (pH=10) to give the desired product. LCMS calculated for C15H18ClFN3 (M+H)+: m/z=294.1; Found: 294.0.

Workup

temperatureAfter cooling to room temperature
temperatureThe reaction was heated at 65° C. overnight
temperaturecooled to room temperature
customquenched with sat. NaHCO3 solution
extractionextracted with Ethyl acetate
dry with materialThe combined organic layers were dried over MgSO4
concentrationconcentrated
custompurified on a preparative LCMS (pH=10)

Sources & evidence

ORD record: ord-4a1a84bb0d614468b185618de32397be
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08680108B2

Reaction notes

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