Dimethylformamide → n-(2-Amino-4-fluorophenyl)-6-(3-(2-(((5-fluoro-2-oxoindolin-3-ylidene)-hydrazono)methyl)-3,5-dimethyl-1h-pyrrole-4-carboxamido)propylamino)nicotinamide

HRID 1695044Notes

Reaction equation

HRID 1695044 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2C(=[CH:9][CH:10]=1)NC(=O)[C:5]2=[N:12][N:13]=CC1(C)CC(C)(C(O)=O)CN1.Cl.C(N=C=NCCCN(C)C)C.[OH:37][C:38]1C2N=NNC=2[CH:41]=[CH:40][CH:39]=1.C([N:49]([CH2:52][CH3:53])[CH2:50][CH3:51])C.[NH2:54][C:55]1[CH:60]=[C:59]([F:61])[CH:58]=[CH:57][C:56]=1[NH:62][C:63](=[O:75])[C:64]1[CH:69]=[CH:68][C:67]([NH:70][CH2:71][CH2:72][CH2:73][NH2:74])=[N:66][CH:65]=1.[CH3:76][N:77]([CH:79]=[O:80])C>[Cl-].[Na+].O>[NH2:54][C:55]1[CH:60]=[C:59]([F:61])[CH:58]=[CH:57][C:56]=1[NH:62][C:63](=[O:75])[C:64]1[CH:69]=[CH:68][C:67]([NH:70][CH2:71][CH2:72][CH2:73][NH:74][C:38]([C:39]2[C:40]([CH3:41])=[C:52]([CH:53]=[N:13][N:12]=[C:5]3[C:4]4[C:76](=[CH:9][CH:10]=[C:2]([F:1])[CH:3]=4)[NH:77][C:79]3=[O:80])[NH:49][C:50]=2[CH3:51])=[O:37])=[N:66][CH:65]=1

Participants

8

Reactant 6

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 57993745N-(2-amino-4-fluorophenyl)-6-(3-aminopropylamino)nicotinamideHCID 1372525122-(((5-Fluoro-2-oxoindolin-3-ylidene)hydrazono)methyl)-2,4-dimethyl-1H-pyrrole-4-carboxylic acidHCID 178418300HCID 178418300, compound

Product 1

HCID 136510511n-(2-Amino-4-fluorophenyl)-6-(3-(2-(((5-fluoro-2-oxoindolin-3-ylidene)-hydrazono)methyl)-3,5-dimethyl-1h-pyrrole-4-carboxamido)propylamino)nicotinamideYield 72%

Reagents, catalysts & solvents 1

HCID 57417360Sodium chloride; waterSolvent

Procedure

2-(((5-Fluoro-2-oxoindolin-3-ylidene)hydrazono)methyl)-2,4-dimethyl-1H-pyrrole-4-carboxylic acid (328 mg, 1 mmol) and 8 ml of DMF were stirred at room temperature while 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (384 mg, 2 mmol), hydroxybenzotriazole (162 mg, 1.2 mmol), triethylamine (404 mg, 4 mmol) and N-(2-amino-4-fluorophenyl)-6-(3-aminopropylamino)nicotinamide (318 mg, 1.05 mmol) were added. The mixture was stirred for 20 hours at room temperature. The mixture was diluted with 400 mL of brine. The solids were collected by vacuum filtration, washed with water and dried under vacuum to give the title compound (441 mg, 72%) as a red solid. 1H NMR (DMSO-d6)δ1.77 (m, 2H, CH2), 2.36 (s, 3H, pyrrole-CH3), 2.45 (s, 3H, pyrrole-CH3), 3.29 (m, 2H, CH2), 3.38 (m, 2H, CH2), 5.18 (s, 2H, benzene-NH2), 6.32 (m, 1H), 6.51 (m, 2H), 6.85 (m, 1H), 7.06 (m, 1H), 7.20 (m, 2H), 7.71 (s, 1H), 7.90 (d, J=8.0 Hz, 1H), 8.33 (d, J=8.0 Hz, 1H), 8.64 (s, 2H), 9.29 (s, 1H, benzene-NH), 10.73 (s, 1H, indolinone-NH), 11.84 (s, 1H, pyrrole-NH). LC-MS (m/z) 614 (M+1).

Workup

  1. additionwere added
  2. filtrationThe solids were collected by vacuum filtration
  3. washwashed with water
  4. customdried under vacuum

Sources & evidence

ORD record
ord-b06238ed5d9a4c26871073b6939f58f1
Source dataset
uspto-grants-2012_04
Patent number
US08158656B2

Reaction notes

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