Hydrochloric Acid → HCID 44233345, compound

HRID 81466Notes

Reaction equation

HRID 81466 reaction equation
[C:1]1([Mg]Br)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:9][C:10]1[N:21]=[CH:20][C:19]([C:22]2[CH:27]=[C:26]([CH3:28])[CH:25]=[C:24]([Cl:29])[CH:23]=2)=[CH:18][C:11]=1[C:12](N(OC)C)=[O:13].Cl>C1COCC1>[NH2:9][C:10]1[C:11]([C:12]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[O:13])=[CH:18][C:19]([C:22]2[CH:27]=[C:26]([CH3:28])[CH:25]=[C:24]([Cl:29])[CH:23]=2)=[CH:20][N:21]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 86634545HCID 86634545, compoundHCID 178418255HCID 178418255, compound2×

Product 1

HCID 44233345HCID 44233345, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

A solution of 1M phenyl magnesium bromide in THF (0.79 ml, 0.79 mmol) is added dropwise to a solution of 2-amino-5-(3-chloro-5-methyl-phenyl)-N-methoxy-N-methyl-nicotinamide (intermediate GB) (0.08 g, 0.26 mmol) in THF (3 ml) at 0° C. The resulting solution is stirred at 0° C. for 30 minutes. 1M Phenyl magnesium bromide in THF (0.79 ml, 0.79 mmols) is added dropwise and the solution stirred for a further 30 minutes at 0° C. 2.5M HCl (10 ml) is added and the product extracted with EtOAc, and solvent removed in vacuo. Purification by reverse phase column chromatography (Isolute™ C18, 0-100% MeCN in water −0.1% TFA) yields the title compound. 1H NMR (400 MHz, DMSO-6) δ 8.28 (1H, dd), 7.77 (2H, br s), 7.66-7.59 (4H, m), 7.55-7.51 (2H, m), 7.37 (1H, d), 7.29 (1H, dd), 7.23 (1H, d), 2.23 (3H, s); MS m/z 323 [M+H]+

Workup

  1. stirringthe solution stirred for a further 30 minutes at 0° C
  2. extractionthe product extracted with EtOAc, and solvent
  3. customremoved in vacuo
  4. customPurification by reverse phase column chromatography (Isolute™ C18, 0-100% MeCN in water −0.1% TFA)

Sources & evidence

ORD record
ord-761cc201461940bfa7d9ea5da6c6b00d
Source dataset
uspto-grants-2014_09
Patent number
US08846687B2

Reaction notes

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