m-Aminoacetanilide → 6-(3-Acetamidophenylamino)-4-(thiophen-2-ylmethylamino)nicotinamide

HRID 513279Notes

Reaction equation

HRID 513279 reaction equation
Cl[C:2]1[CH:10]=[C:9]([NH:11][CH2:12][C:13]2[S:14][CH:15]=[CH:16][CH:17]=2)[C:5]([C:6]([NH2:8])=[O:7])=[CH:4][N:3]=1.[NH2:18][C:19]1[CH:20]=[C:21]([CH:26]=[CH:27][CH:28]=1)[NH:22][C:23](=[O:25])[CH3:24].C1(O[Na])C=CC=CC=1.O.O.O.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:23]([NH:22][C:21]1[CH:20]=[C:19]([NH:18][C:2]2[CH:10]=[C:9]([NH:11][CH2:12][C:13]3[S:14][CH:15]=[CH:16][CH:17]=3)[C:5]([C:6]([NH2:8])=[O:7])=[CH:4][N:3]=2)[CH:28]=[CH:27][CH:26]=1)(=[O:25])[CH3:24]

Participants

7

Reactant 4

HCID 7604m-AminoacetanilideHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 584398316-Chloro-4-(thiophen-2-ylmethylamino)nicotinamideHCID 178526975HCID 178526975, compound

Product 1

HCID 675018936-(3-Acetamidophenylamino)-4-(thiophen-2-ylmethylamino)nicotinamideYield 12.7%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 6-chloro-4-(thiophen-2-ylmethylamino)nicotinamide (100 mg, 0.373 mmol), 3′-aminoacetanilide (65 mg, 0.433 mmol), PhONa trihydrate (80 mg, 0.471 mmol), xantphos (30 mg, 0.051 mmol) and Pd2 dba3 (20 mg, 0.021 mmol) in dioxane (2 mL) was degassed with Ar, then was stirred at 110 C for 3 h. Water and EtOAc were added. The mixture was filtered. The organic phase was separated, washed with aq. 1N NaOH, dried over Na2SO4, concentrated in vacuo. The residue was purified by HPLC to give the titled compound (18 mg). MS 382.3 (M+H); UV 251.0 nm; t 0.465 min.

Workup

  1. customwas degassed with Ar
  2. additionWater and EtOAc were added
  3. filtrationThe mixture was filtered
  4. customThe organic phase was separated
  5. washwashed with aq. 1N NaOH
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by HPLC

Sources & evidence

ORD record
ord-45f19abe6290493a8746b619ab6f4dfa
Source dataset
uspto-grants-2015_08
Patent number
US09102625B2

Reaction notes

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