4-Fluoro-3-methylanisole → (2-Amino-6-chloro-pyridin-3-yl)-(5-fluoro-2-methoxy-4-methyl-phenyl)-methanone

HRID 30140

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[CH3:10].C([Li])CCC.[NH2:16][C:17]1[N:28]=[C:27]([Cl:29])[CH:26]=[CH:25][C:18]=1[C:19](N(OC)C)=[O:20]>O1CCCC1>[NH2:16][C:17]1[C:18]([C:19]([C:6]2[CH:7]=[C:2]([F:1])[C:3]([CH3:10])=[CH:4][C:5]=2[O:8][CH3:9])=[O:20])=[CH:25][CH:26]=[C:27]([Cl:29])[N:28]=1

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of 4-fluoro-3-methylanisole (0.75 mL, 802 mg, 5.55 mmol, Aldrich 97%) in anhydrous tetrahydrofuran (5 mL) at −78° C., was added slowly a solution of n-butyllithium in hexanes (2.5 M, 2.22 mL, 5.55 mmol, Aldrich). The reaction was stirred at −78° C. for 10 mins before it was allowed to warm to −25-0° C. and stirred for 1.5 hour. The resulting aryllithium reagent was cooled back to −78° C. and reacted with 2-Amino-6-chloro-N-methoxy-N-methyl-nicotinamide as described in Example 7 to give (2-Amino-6-chloro-pyridin-3-yl)-(5-fluoro-2-methoxy-4-methyl-phenyl)-methanone as an off-white solid. HRMS, observed: 295.0645, Calcd for (M+H)+: 295.0644.

Workup

temperatureto warm to −25-0° C.
stirringstirred for 1.5 hour

Sources & evidence

ORD record: ord-4ff8d6755b9648f4a7cc36b0197ef249
Source dataset: uspto-grants-2008_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07423051B2

Linked notes

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