Cesium carbonate → 2-[[2-[(1,3-dimethylpyrazol-4-yl)amino]-5-(trifluoromethyl)-4-pyridyl]amino]-6-methoxy-N-methyl-benzamide

HRID 1045941Notes

Reaction equation

HRID 1045941 reaction equation
[NH2:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]([O:12][CH3:13])[C:3]=1[C:4]([NH:6][CH3:7])=[O:5].[CH3:14][N:15]1[CH:19]=[C:18]([NH:20][C:21]2[CH:26]=[C:25](I)[C:24]([C:28]([F:31])([F:30])[F:29])=[CH:23][N:22]=2)[C:17]([CH3:32])=[N:16]1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C(Cl)Cl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:14][N:15]1[CH:19]=[C:18]([NH:20][C:21]2[CH:26]=[C:25]([NH:1][C:2]3[CH:11]=[CH:10][CH:9]=[C:8]([O:12][CH3:13])[C:3]=3[C:4]([NH:6][CH3:7])=[O:5])[C:24]([C:28]([F:30])([F:29])[F:31])=[CH:23][N:22]=2)[C:17]([CH3:32])=[N:16]1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 122648202-amino-6-methoxy-N-methylbenzamideHCID 56951658N-(1,3-dimethylpyrazol-4-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine

Product 1

HCID 446088842-[[2-[(1,3-dimethylpyrazol-4-yl)amino]-5-(trifluoromethyl)-4-pyridyl]amino]-6-methoxy-N-methyl-benzamideYield 52.5%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of 2-amino-6-methoxy-N-methylbenzamide (2.48 g, 13.8 mmol), N-(1,3-dimethylpyrazol-4-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine (2.63 g, 6.88 mmol), palladium(II) acetate (0.077 g, 0.34 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (0.398 g, 0.69 mmol) and cesium carbonate (4.48 g, 13.77 mmol) in dioxane (37 mL) was degassed with argon and stirred at 100° C. for 3 hours. The reaction mixture was concentrated to dryness, diluted with EtOAc (80 ml), washed with water (1×50 ml) and brine, dried over magnesium sulfate and concentrated to afford an oil. The crude product was purified by flash chromatography on silica gel eluting with EtOAc and then 3 to 8% MeOH in EtOAc. The solvent was evaporated to dryness to afford a foam which was dissolved in DCM (12 ml). A solid formed after a few minutes and this was filtered and dried to give the title compound as a white solid (1.570 g, 52.5%). 1H NMR spectrum (500 MHz, CDCl3): 2.15 (s, 3H), 2.97 (d, 3H), 3.79 (s, 3H), 3.91 (s, 3H), 5.99 (s, 1H), 6.32 (s, 1H), 6.56 (d, 1H), 7.05 (d, 1H), 7.20 (dd, 1H), 7.34 (s, 1H), 7.44 (q, 1H), 8.23 (s, 1H), 10.56 (s, 1H); Mass spectrum: ESI+435.

Workup

  1. customwas degassed with argon
  2. concentrationThe reaction mixture was concentrated to dryness
  3. additiondiluted with EtOAc (80 ml)
  4. washwashed with water (1×50 ml) and brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated
  7. customto afford an oil
  8. customThe crude product was purified by flash chromatography on silica gel eluting with EtOAc
  9. customThe solvent was evaporated to dryness
  10. customto afford a foam which
  11. customA solid formed after a few minutes
  12. filtrationthis was filtered
  13. customdried

Sources & evidence

ORD record
ord-b6dfbc80d4e8486fad341e173c604738
Source dataset
uspto-grants-2013_10
Patent number
US08569298B2

Reaction notes

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