Ammonium Acetate → (3S)-1-[7-(1-aminoethyl)-5-chloroquinolin-8-yl]piperidin-3-ol

HRID 1192555Notes

Reaction equation

[Cl:1][C:2]1[CH:11]=[C:10]([C:12](=O)[CH3:13])[C:9]([N:15]2[CH2:20][CH2:19][CH2:18][C@H:17]([OH:21])[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:28].[Na+]>CO.C(#N)C>[NH2:28][CH:12]([C:10]1[C:9]([N:15]2[CH2:20][CH2:19][CH2:18][C@H:17]([OH:21])[CH2:16]2)=[C:8]2[C:3]([CH:4]=[CH:5][CH:6]=[N:7]2)=[C:2]([Cl:1])[CH:11]=1)[CH3:13]

Participants

Conditions

Temperature: 65 °C

Procedure

A mixture of 1-{5-chloro-8-[(3S)-3-hydroxypiperidin-1-yl]quinolin-7-yl}ethanone (18 mg, 0.059 mmol) and ammonium acetate (45.5 mg, 0.591 mmol) in methanol (0.33 mL) and acetonitrile (0.34 mL) was heated at 65° C. in a sealed tube for 30 minutes. After cooling to room temperature, sodium cyanoborohydride (7.42 mg, 0.118 mmol). The reaction was heated at 65° C. for another 4 hours, then cooled to room temperature and quenched with sat. sodium bicarbonate, extracted with dichloromethane. The combined extracts were dried over magnesium sulfate and evaporated to dryness. The crude amine was used directly in the next step. LCMS calculated for C16H21ClN3O (M+H)+: m/z=306.1; Found: 306.1.

Workup

temperatureAfter cooling to room temperature
temperatureThe reaction was heated at 65° C. for another 4 hours
temperaturecooled to room temperature
customquenched with sat. sodium bicarbonate
extractionextracted with dichloromethane
dry with materialThe combined extracts were dried over magnesium sulfate
customevaporated to dryness

Sources & evidence

ORD record: ord-6425e4d84404484286e203a433db099b
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08680108B2

Reaction notes

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