Diisopropylamine → 4-(4-Bromo-2-fluorophenylamino)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid

HRID 15905

Reaction equation

N(C(C)C)C(C)C.[Li]CCCC.[Br:13][C:14]1[CH:19]=[CH:18][C:17]([NH2:20])=[C:16]([F:21])[CH:15]=1.Cl[C:23]1[C:24]([C:31]([OH:33])=[O:32])=[CH:25][N:26]([CH3:30])[C:27](=[O:29])[CH:28]=1>C1COCC1>[Br:13][C:14]1[CH:19]=[CH:18][C:17]([NH:20][C:23]2[C:24]([C:31]([OH:33])=[O:32])=[CH:25][N:26]([CH3:30])[C:27](=[O:29])[CH:28]=2)=[C:16]([F:21])[CH:15]=1

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of i-Pr2NH (0.39 mL, 2.80 mmol) in THF (4 mL) at 0° C. was added n-BuLi (1.1 mL, 2.80 mmol, 2.5 M solution in hexanes). After stirring 15 minutes, the mixture was cooled to −78° C. 4-Bromo-2-fluorophenylamine (0.38 g, 2.0 mmol) was added. After vigorous stirring for 10 minutes, a mixture of the 4-chloro-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid (0.15 g, 0.80 mmol) in THF (5 mL) was added. The dry-ice bath was removed after 30 minutes, and the reaction mixture was stirred for 17 hours at room temperature. The reaction mixture was treated with a 10% aqueous HCl solution (15 mL), extracted with EtOAc, dried (MgSO4), and concentrated. Trituration with methylene chloride gave 0.21 g (77%) desired product. MS APCI (−) m/z 339, 341 (M−, Br pattern) detected; 1H NMR (400 MHz, DMSO-d6) δ 9.61 (s, 1H), 8.53 (s, 1H), 7.69 (dd, 1H), 7.46 (m, 2H), 3.41 (s, 3H).

Workup

stirringAfter vigorous stirring for 10 minutes
additionwas added
customThe dry-ice bath was removed after 30 minutes
stirringthe reaction mixture was stirred for 17 hours at room temperature
additionThe reaction mixture was treated with a 10% aqueous HCl solution (15 mL)
extractionextracted with EtOAc
dry with materialdried (MgSO4)
concentrationconcentrated

Sources & evidence

ORD record: ord-a1b145c11bfd4da983cfc7af5f4fc7eb
Source dataset: uspto-grants-2010_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07732616B2

Linked notes

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