2-Hydroxyquinoline-3-carbaldehyde → 7-Fluoro-1-[2-(4-{[(2-oxo-1,2-dihydroquinolin-3-yl)methyl]amino}piperidin-1-yl)ethyl]quinoxalin-2(1H)-one

HRID 1644470Notes

Reaction equation

[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][N:10]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([F:20])[CH:18]=3)[N:13]=[CH:12][C:11]2=[O:21])[CH2:4][CH2:3]1.[O:22]=[C:23]1[C:32]([CH:33]=O)=[CH:31][C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[NH:24]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO>[F:20][C:17]1[CH:18]=[C:19]2[C:14]([N:13]=[CH:12][C:11](=[O:21])[N:10]2[CH2:9][CH2:8][N:5]2[CH2:4][CH2:3][CH:2]([NH:1][CH2:33][C:32]3[C:23](=[O:22])[NH:24][C:25]4[C:30]([CH:31]=3)=[CH:29][CH:28]=[CH:27][CH:26]=4)[CH2:7][CH2:6]2)=[CH:15][CH:16]=1

Participants

Conditions

Temperature: 0 °C

Procedure

A mixture of 1-[2-(4-aminopiperidin-1-yl)ethyl]-7-fluoroquinoxalin-2(1H)-one (Intermediate 140, 130 mg, 0.448 mmol), 2-oxo-1,2-dihydroquinoline-3-carbaldehyde (65 mg, 0.448 mmol) and 3 Å molecular sieves (100 mg) in methanol (6.0 mL) was heated at reflux for 2.5 hours under nitrogen atmosphere. It was cooled to 0° C. and sodium triacetoxy borohydride (189.5 mg, 0.996 mmol) was added and the mixture was allowed to warm to room temperature and stirred overnight. The mixture was filtered and purified through silica gel plug (eluting with 15% methanol in methylene chloride) to give title compound (71 mg).

Workup

temperaturewas heated
temperatureat reflux for 2.5 hours under nitrogen atmosphere
temperatureto warm to room temperature
filtrationThe mixture was filtered
custompurified through silica gel plug (eluting with 15% methanol in methylene chloride)

Sources & evidence

ORD record: ord-4b25cfe406b74ff5bc803b02b87a1165
Source dataset: uspto-grants-2012_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08124602B2

Reaction notes

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