N-Methyl-o-phenylenediamine → N-(2-Amino-phenyl)-2-(2,5-dichloro-phenoxy)-N-methyl-nicotinamide

HRID 1877397Notes

Reaction equation

HRID 1877397 reaction equation
[Cl:1][C:2]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:3]=1[O:4][C:5]1[N:13]=[CH:12][CH:11]=[CH:10][C:6]=1[C:7]([OH:9])=O.C(N(C(C)C)C(C)C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:52][NH:53][C:54]1[C:55]([NH2:60])=[CH:56][CH:57]=[CH:58][CH:59]=1>CN(C=O)C>[NH2:60][C:55]1[CH:56]=[CH:57][CH:58]=[CH:59][C:54]=1[N:53]([CH3:52])[C:7](=[O:9])[C:6]1[CH:10]=[CH:11][CH:12]=[N:13][C:5]=1[O:4][C:3]1[CH:14]=[C:15]([Cl:18])[CH:16]=[CH:17][C:2]=1[Cl:1]

Participants

6

Reactant 4

HCID 78498N-Methyl-o-phenylenediamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 167959962-(2,5-Dichloro-phenoxy)-nicotinic acid

Product 1

HCID 46195127N-(2-Amino-phenyl)-2-(2,5-dichloro-phenoxy)-N-methyl-nicotinamideYield 47.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-(2,5-dichloro-phenoxy)-nicotinic acid (50 mg, 0.18 mmol, 1.0 equiv; Example 31, Step 1) in anhydrous DMF (2 mL) was added N-ethyldiisopropylamine (116 mg, 154 μL, 0.90 mmol, 5.0 equiv; [CAS RN 7087-68-5]) and HATU (82 mg, 0.22 mmol, 1.2 equiv; [CAS RN 148893-10-1]) and the reaction mixture stirred at rt for 30 min. After addition of N-methyl-benzene-1,2-diamine (26.9 mg, 0.22 mmol, 1.2 equiv; [CAS RN 4760-34-3]) stirring was continued at rt for 90 min. Removal of the solvent under reduced pressure and purification by silica column chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of heptane/ethyl acetate afforded 33 mg (47%) of the title compound as a white solid. MS (ISP): 388.0 [M+H]+.

Workup

  1. stirringstirring
  2. waitwas continued at rt for 90 min
  3. customRemoval of the solvent
  4. customunder reduced pressure and purification by silica column chromatography
  5. washeluting with a gradient of heptane/ethyl acetate

Sources & evidence

ORD record
ord-2be3aa02b5674e7ca1e960157161715c
Source dataset
uspto-grants-2012_11
Patent number
US08309734B2

Reaction notes

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