Sodium hydride → 8-(cyclopentyloxy)-4-(3,5-dichloropyridin-4-ylamino)-3-fluoro-7-methoxy-2H-chromen-2-one

HRID 20643Notes

Reaction equation

[H-].[Na+].[NH2:3][C:4]1[C:13]2[C:8](=[C:9]([O:16][CH:17]3[CH2:21][CH2:20][CH2:19][CH2:18]3)[C:10]([O:14][CH3:15])=[CH:11][CH:12]=2)[O:7][C:6](=[O:22])[C:5]=1[F:23].[Cl:24][C:25]1[CH:26]=[N:27][CH:28]=[C:29]([Cl:32])[C:30]=1Cl.OP([O-])(O)=O.[K+]>CS(C)=O>[CH:17]1([O:16][C:9]2[C:10]([O:14][CH3:15])=[CH:11][CH:12]=[C:13]3[C:8]=2[O:7][C:6](=[O:22])[C:5]([F:23])=[C:4]3[NH:3][C:30]2[C:29]([Cl:32])=[CH:28][N:27]=[CH:26][C:25]=2[Cl:24])[CH2:21][CH2:20][CH2:19][CH2:18]1

Participants

Conditions

Temperature: 50 °C

Procedure

Sodium hydride (40 mg, 60%, 1.0 mmol) was added to a solution of 4-amino-8-(cyclopentyloxy)-3-fluoro-7-methoxy-2H-chromen-2-one (95 mg, 0.32 mmol), 3,4,5-trichloropyridine (118 mg, 0.65 mmol), and DMSO (3 mL) at rt under N2. After 1.5 h, the reaction was heated at 50° C. for 2 h and then 70° C. for 2 h. The reaction was allowed to cool to rt, poured into 1M KH2PO4 (30 mL) and extracted with ethyl acetate (40 mL×2). The combined extracts were dried, filtered, concentrated, and purified by silica gel chromatography (7:3→0:1; hexanes:ethyl acetate) to give 8-(cyclopentyloxy)-4-(3,5-dichloropyridin-4-ylamino)-3-fluoro-7-methoxy-2H-chromen-2-one: 1H NMR (400 MHz, DMSO-d6): δ 9.36 (s, 1H), 8.70 (s, 2H), 7.90 (d, 1H), 7.25 (d, 1H), 4.84 (m, 1H), 3.90 (s, 3H), 1.90-1.45 (m, 8H); MS (ESI): 438.8.

Workup

wait70° C. for 2 h
temperatureto cool to rt
extractionextracted with ethyl acetate (40 mL×2)
customThe combined extracts were dried
filtrationfiltered
concentrationconcentrated
custompurified by silica gel chromatography (7:3→0:1; hexanes:ethyl acetate)

Sources & evidence

ORD record: ord-3c1adbf11de7412696782c5250025b43
Source dataset: uspto-grants-2010_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07745646B2

Reaction notes

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