Cesium carbonate → N-methyl-2-[[2-[(2-methylpyrazol-3-yl)amino]-5-(trifluoromethyl)-4-pyridyl]amino]benzamide

HRID 1045946

Reaction equation

HRID 1045946 reaction equation
Cl[C:2]1[CH:7]=[C:6]([NH:8][C:9]2[CH:18]=[CH:17][CH:16]=[CH:15][C:10]=2[C:11]([NH:13][CH3:14])=[O:12])[C:5]([C:19]([F:22])([F:21])[F:20])=[CH:4][N:3]=1.[CH3:23][N:24]1[C:28]([NH2:29])=[CH:27][CH:26]=[N:25]1.C(=O)([O-])[O-].[Cs+].[Cs+].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>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:14][NH:13][C:11](=[O:12])[C:10]1[CH:15]=[CH:16][CH:17]=[CH:18][C:9]=1[NH:8][C:6]1[C:5]([C:19]([F:22])([F:21])[F:20])=[CH:4][N:3]=[C:2]([NH:29][C:28]2[N:24]([CH3:23])[N:25]=[CH:26][CH:27]=2)[CH:7]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 1369272-Methyl-2H-pyrazol-3-ylamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 566553282-[2-Chloro-5-(trifluoromethyl)pyridin-4-ylamino]-N-methylbenzamide

Product 1

HCID 44609203N-methyl-2-[[2-[(2-methylpyrazol-3-yl)amino]-5-(trifluoromethyl)-4-pyridyl]amino]benzamideYield 52.9%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

2-[[2-chloro-5-(trifluoromethyl)pyridin-4-yl]amino]-N-methylbenzamide (100 mg, 0.30 mmol, Example 2.01), 1-methylpyrazol-5-amine (58.9 mg, 0.61 mmol), cesium carbonate (119 mg, 0.36 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (28.1 mg, 0.05 mmol) and palladium(II) acetate (5.45 mg, 0.02 mmol) were suspended in dioxane (1.5 mL) in a sealed tube. The reaction was degased, purged with nitrogen and heated to 100° C. for 18 hours. The reaction mixture was filtered and purified by preparative HPLC using a Waters X-Bridge reverse-phase column (C-18, 5 microns silica, 19 mm diameter, 100 mm length, flow rate of 40 ml/minute) and decreasingly polar mixtures of water (containing 0.2% ammonium carbonate) and acetonitrile as eluent. The fractions containing the desired compound were evaporated to dryness to afford the title compound (62 mg, 52.4%) as a pale orange solid. 1H NMR spectrum (500 MHz, DMSO): 2.77 (d, 3H), 3.63 (s, 3H), 6.21 (d, 1H), 6.70 (s, 1H), 7.13 (ddd, 1H), 7.32 (d, 1H), 7.49 (ddd, 1H), 7.55 (d, 1H), 7.71 (dd, 1H), 8.25 (s, 1H), 8.68 (q, 1H), 9.03 (s, 1H), 10.20 (s, 1H); Mass spectrum: ESI+ MH+ 391.

Workup

  1. customThe reaction was degased
  2. custompurged with nitrogen
  3. filtrationThe reaction mixture was filtered
  4. custompurified by preparative HPLC
  5. additionThe fractions containing the desired compound
  6. customwere evaporated to dryness

Sources & evidence

ORD record
ord-6ceeb2a5864d4a7f84ecce1c51f727ee
Source dataset
uspto-grants-2013_10
Patent number
US08569298B2

Linked notes

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