O-Phenylenediamine → N-(2-aminophenyl)-3-fluoro-5-[(2-fluoro-4-iodophenyl)amino]isonicotinamide

HRID 2167227Notes

Reaction equation

HRID 2167227 reaction equation
[F:1][C:2]1[CH:10]=[N:9][CH:8]=[C:7]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([I:18])=[CH:14][C:13]=2[F:19])[C:3]=1[C:4]([OH:6])=O.[NH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[NH2:27].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>CN(C=O)C>[NH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[NH:27][C:4](=[O:6])[C:3]1[C:7]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([I:18])=[CH:14][C:13]=2[F:19])=[CH:8][N:9]=[CH:10][C:2]=1[F:1]

Participants

6

Reactant 4

HCID 7243O-PhenylenediamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 670811353-Fluoro-5-[(2-fluoro-4-iodophenyl)amino]isonicotinic acid2×

Product 1

HCID 67513903N-(2-aminophenyl)-3-fluoro-5-[(2-fluoro-4-iodophenyl)amino]isonicotinamideYield 55.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

100 mg of 3-fluoro-5-[(2-fluoro-4-iodophenyl)amino]isonicotinic acid (0.266 mmol, 1 eq.; Intermediate 1A) were suspended in 2 mL of DMF and then 28,754 mg 1,2-diaminobenzene (0.266 mmol, 1 eq.), 215,339 mg of HATU (0.566 mmol, 2.13 eq.) and 73,196 mg of N,N-Diisopropylethylamine (0.566 mmol, 2.13 eq.) were added and stirring was continued at 50° C. temperature for 18 h. The reaction mixture was partitioned between 20 ml of ethyl acetate and 20 ml of brine. The aqueouse layer was reextracted twice with 20 ml of ethyl acetate each. The combined organic layers were dried over a silicone filter and concentrated in vacuo. The residue was purified by flash chromatography to afford 69 mg of the target compound in 72% UV-purity. This material was used for the next step without further purification.

Workup

  1. customwas continued at 50° C.
  2. customfor 18 h
  3. customThe reaction mixture was partitioned between 20 ml of ethyl acetate and 20 ml of brine
  4. dry with materialThe combined organic layers were dried over a silicone
  5. filtrationfilter
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-005a8b7c158e4f2ba6bc142243f0b706
Source dataset
uspto-grants-2015_06
Patent number
US09045429B2

Reaction notes

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