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 255342Notes

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-9847802978ff4a55817ee19ba6ca6ede
Source dataset: uspto-grants-2011_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07875715B2

Reaction notes

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