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

HRID 20633Notes

Reaction equation

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

Participants

Conditions

Temperature: 60 °C

Procedure

Sodium hydride (8 mg, 60%, 0.2 mmol) was added to a solution of 4-amino-8-(cyclopropylmethoxy)-3-ethyl-7-methoxy-2H-chromen-2-one (24 mg, 0.083 mmol) and DMSO (3 mL) at rt under N2. After 5 min. 3,4,5-trichloropyridine (19 mg, 0.1 mmol) was added, and the reaction was heated at 60° C. After 2 h, more 3,4,5-trichloropyridine (25 mg, 0.14 mmol) was added followed by more sodium hydride (15 mg, 60%, 0.38 mmol). After an additional 2 h at 60° C., the reaction was poured into 1M KH2PO4 (40 mL) and extracted with ethyl acetate (40 mL×2). The combined extracts were dried, filtered, concentrated, and purified by silica gel chromatography (7:3→1:4; hexanes:ethyl acetate) to give 8-(cyclopropylmethoxy)-4-(3,5-dichloropyridin-4-ylamino)-3-ethyl-7-methoxy-2H-chromen-2-one: MS (ESI): 434.8.

Workup

waitAfter 2 h
waitAfter an additional 2 h at 60° C.
extractionextracted with ethyl acetate (40 mL×2)
customThe combined extracts were dried
filtrationfiltered
concentrationconcentrated
custompurified by silica gel chromatography (7:3→1:4; hexanes:ethyl acetate)

Sources & evidence

ORD record: ord-04c30d57ca8145fe86e11537f88b03fd
Source dataset: uspto-grants-2010_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07745646B2

Reaction notes

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