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

HRID 1695043Notes

Reaction equation

HRID 1695043 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])/[C:5]/2=[CH:12]\[C:13]1[NH:17][C:16]([CH3:18])=[C:15]([C:19]([OH:21])=O)[C:14]=1[CH3:22].Cl.C(N=C=NCCCN(C)C)C.OC1C2N=NNC=2C=CC=1.C(N(CC)CC)C.[NH2:52][C:53]1[CH:58]=[C:57]([F:59])[CH:56]=[CH:55][C:54]=1[NH:60][C:61](=[O:73])[C:62]1[CH:67]=[CH:66][C:65]([NH:68][CH2:69][CH2:70][CH2:71][NH2:72])=[N:64][CH:63]=1>[Cl-].[Na+].O.CN(C=O)C>[NH2:52][C:53]1[CH:58]=[C:57]([F:59])[CH:56]=[CH:55][C:54]=1[NH:60][C:61](=[O:73])[C:62]1[CH:67]=[CH:66][C:65]([NH:68][CH2:69][CH2:70][CH2:71][NH:72][C:19]([C:15]2[C:14]([CH3:22])=[C:13](/[CH:12]=[C:5]3\[C:6](=[O:11])[NH:7][C:8]4[C:4]\3=[CH:3][C:2]([F:1])=[CH:10][CH:9]=4)[NH:17][C:16]=2[CH3:18])=[O:21])=[N:64][CH:63]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10979489Sunitinib acidHCID 57993745N-(2-amino-4-fluorophenyl)-6-(3-aminopropylamino)nicotinamideHCID 178418300HCID 178418300, compound

Product 1

HCID 44538461(z)-n-(2-Amino-4-fluorophenyl)-6-(3-(2-((5-fluoro-2-oxoindolin-3-ylidene)-methyl)-3,5-dimethyl-1h-pyrrole-4-carboxamido)propylamino)nicotinamideYield 78%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

5-(5-Fluoro-2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (300 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 (456 mg, 78%) as a yellow solid. 1H NMR (DMSO-d6)δ 1.78 (m, 2H, CH2), 2.42 (s, 3H, pyrrole-CH3), 2.44 (s, 3H, pyrrole-CH3), 3.30 (m, 2H, CH2), 3.38 (m, 2H, CH2), 5.18 (s, 2H, benzene-NH2), 6.33 (m, 1H), 6.51 (m, 2H), 6.84 (m, 1H), 6.90 (m, 1H), 7.06 (t, J=8.0 Hz, 1H), 7.20 (s, 1H), 7.71˜7.76 (m, 3H), 7.91 (d, J=8.0 Hz, 1H), 8.63 (s, 1H), 9.30 (s, 1H, benzene-NH), 10.90 (s, 1H, indolinone-NH), 13.68 (s, 1H, pyrrole-NH). LC-MS (m/z) 586 (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-47bfd48c67124e43954bfbede12de5b4
Source dataset
uspto-grants-2012_04
Patent number
US08158656B2

Reaction notes

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