Sodium hydride → 2-(7-((3,4-Difluorobenzyl)oxy)-1,5-naphthyridin-3-yl)acetamide

HRID 513964

Reaction equation

Br[C:2]1[CH:3]=[N:4][C:5]2[C:10]([CH:11]=1)=[N:9][CH:8]=[C:7]([O:12][CH2:13][C:14]1[CH:19]=[CH:18][C:17]([F:20])=[C:16]([F:21])[CH:15]=1)[CH:6]=2.FC1C=[C:25]([CH2:30][OH:31])C=CC=1F.BrC1C=[N:35]C2C(C=1)=NC=C(Br)C=2.[H-].[Na+]>CN1C(=O)CCC1.O>[F:21][C:16]1[CH:15]=[C:14]([CH:19]=[CH:18][C:17]=1[F:20])[CH2:13][O:12][C:7]1[CH:6]=[C:5]2[C:10]([CH:11]=[C:2]([CH2:25][C:30]([NH2:35])=[O:31])[CH:3]=[N:4]2)=[N:9][CH:8]=1

Participants

Conditions

Temperature: 100 °C

Procedure

3-Bromo-7-((3,4-difluorobenzyl)oxy)-1,5-naphthyridine. To a mixture of (3,4-difluorophenyl)methanol (119 μL, 1.04 mmol) and 3,7-dibromo-1,5-naphthyridine (Intermediate 3, 200 mg, 0.69 mmol) in NMP (1 mL) at 100° C. under a nitrogen atmosphere was added a slurry of sodium hydride (69.45 mg, 1.74 mmol) in NMP (1 mL) dropwise. The solution was allowed to stir at 100° C. for 3 h. Upon completion the reaction was cooled and water was added to afford a solid precipitate. The solid was collected by filtration to give the title compound (130 mg, 53.3%) as a crude brown solid, which used without further purification. 1H NMR (400 MHz, CDCl3) δ 8.93 (s, 1H), 8.82 (d, J=2.5 Hz, 1H), 8.54 (s, 1H), 7.66 (d, J=2.0 Hz, 1H), 7.41-7.31 (m, 1H), 7.27-7.16 (m, 2H), 5.19 (s, 2H). [M+H]=351.1.

Workup

temperatureUpon completion the reaction was cooled
customto afford a solid precipitate
filtrationThe solid was collected by filtration

Sources & evidence

ORD record: ord-d580286de7c34f9b887dd92409e4fd91
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09102674B2

Linked notes

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