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

HRID 2387380Notes

Reaction equation

HRID 2387380 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[N:10]([CH3:19])[C:11](=[O:18])[CH:12]=[CH:13][C:14]=2[C:15]([OH:17])=O)=[C:4]([F:20])[CH:3]=1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[CH:42]1([CH2:45][O:46][NH2:47])[CH2:44][CH2:43]1.CCN(CC)CC>CC(N(C)C)=O.CCOC(C)=O>[CH:42]1([CH2:45][O:46][NH:47][C:15]([C:14]2[CH:13]=[CH:12][C:11](=[O:18])[N:10]([CH3:19])[C:9]=2[NH:8][C:5]2[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][C:4]=2[F:20])=[O:17])[CH2:44][CH2:43]1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 11182605O-(cyclopropylmethyl)hydroxylamineHCID 576369362-(4-Bromo-2-fluorophenylamino)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid

Product 1

HCID 112120152-(4-Bromo-2-fluorophenylamino)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid cyclopropylmethoxy-amideYield 57.1%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Procedure

A mixture of 2-(4-bromo-2-fluorophenylamino)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid (0.022 g, 0.064 mmol), EDCI (0.019 g, 0.097 mmol), and HOBt (0.019 g, 0.097 mmol) in DMA (1 mL) was stirred for 30 minutes at room temperature under N2. O-Cyclopropylmethyl-hydroxylamine (0.017 g, 0.19 mmol) was added followed by Et3N (0.022 mL, 0.016 g, 0.16 mmol). After the reaction mixture was stirred for 16 hours at room temperature, it was diluted with EtOAc and washed with saturated NH4Cl solution, saturated NaHCO3 solution and saturated NaCl. The organic layer was dried (Na2SO4) and concentrated under reduced pressure. Purification by flash column chromatography (methylene chloride/methanol, 20:1) gave 0.015 g (57%) pure desired product as a yellow solid. MS APCI (−) m/z 410, 411 (M−, Br pattern) detected; 1H NMR (400 MHz, DMSO-d6) δ 11.4 (s, 1H), 9.81 (s, 1H), 7.58 (m, 2H), 7.28 (d, 1H), 6.82 (t, 1H), 6.17 (d, 1H), 3.46 (d, 2H), 3.22 (s, 3H), 0.99 (m, 1H), 0.48 (m, 2H), 0.18 (m, 2H).

Workup

  1. stirringAfter the reaction mixture was stirred for 16 hours at room temperature
  2. washwashed with saturated NH4Cl solution, saturated NaHCO3 solution and saturated NaCl
  3. dry with materialThe organic layer was dried (Na2SO4)
  4. concentrationconcentrated under reduced pressure
  5. customPurification by flash column chromatography (methylene chloride/methanol, 20:1)

Sources & evidence

ORD record
ord-6cf4db0ef462452aa9ab8c2737d68a99
Source dataset
uspto-grants-2012_09
Patent number
US08268852B2

Reaction notes

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