Cesium carbonate → 2-{[5-Chloro-2-({1-ethyl-3-[2-(1-pyrrolidinyl)ethyl]-1H-pyrazol-5-yl}amino)-4-pyridinyl]amino}-N-methylbenzamide

HRID 62500

Reaction equation

HRID 62500 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]([Cl:19])=[CH:4][N:3]=1.[CH2:20]([N:22]1[C:26]([NH2:27])=[CH:25][C:24]([CH2:28][CH2:29][N:30]2[CH2:34][CH2:33][CH2:32][CH2:31]2)=[N:23]1)[CH3:21].C(=O)([O-])[O-].[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[Cl:19][C:5]1[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])=[CH:7][C:2]([NH:27][C:26]2[N:22]([CH2:20][CH3:21])[N:23]=[C:24]([CH2:28][CH2:29][N:30]3[CH2:34][CH2:33][CH2:32][CH2:31]3)[CH:25]=2)=[N:3][CH:4]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 575168912-[(2,5-Dichloro-4-pyridinyl)amino]-N-methylbenzamideHCID 575169001-ethyl-3-[2-(1-pyrrolidinyl)ethyl]-1H-pyrazol-5-amine

Product 1

HCID 462150962-{[5-Chloro-2-({1-ethyl-3-[2-(1-pyrrolidinyl)ethyl]-1H-pyrazol-5-yl}amino)-4-pyridinyl]amino}-N-methylbenzamideYield 39.2%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
170 °C

Procedure

To a 5-mL microwave tube were added 2-[(2,5-dichloro-4-pyridinyl)amino]-N-methylbenzamide (100 mg, 0.338 mmol), 1-ethyl-3-[2-(1-pyrrolidinyl)ethyl]-1H-pyrazol-5-amine (70.3 mg, 0.338 mmol), cesium carbonate (330 mg, 1.013 mmol), and 1,4-dioxane (2 mL), and the mixture was degassed by bubbling nitrogen through for 15 min. Palladium (II) acetate (3.79 mg, 0.017 mmol) and BINAP (21.03 mg, 0.034 mmol) were added, and the reaction mixture was heated at 170° C. with stirring under microwave conditions for 40 min. The reaction mixture was filtered and concentrated. The residue was purified by using RP-HPLC under basic conditions (Gemini 5u C18(2) 110A, AXI. 50×30.00 mm 5 micron: 7.3-minute run, 47 mL/min, 40% ACN/H2O, 0.1% NH4OH to 90% ACN/H2O, 0.1% NH4OH with UV detection at 254 nm) to give the title compound (62 mg). MS: (M+H)+=468.1. 1H NMR (400 MHz, DMSO-d6) ppm 1.21 (t, J=7.2 Hz, 3 H), 1.67 (m, 4H), 2.45 (m, 4), 2.60 (m, 4H), 2.77 (d, J=4.0 Hz, 3H), 3.89 (q, J=7.2 Hz, 2H), 6.03 (s, 1H), 6.74 (s, 1H), 7.11 (m, 1H), 7.49 (m, 1H), 7.54 (m, 1H), 7.71 (d, J=7.2 Hz, 1H), 8.00 (s, 1H).

Workup

  1. customthe mixture was degassed
  2. customby bubbling nitrogen through for 15 min
  3. filtrationThe reaction mixture was filtered
  4. concentrationconcentrated
  5. customThe residue was purified
  6. customunder basic conditions (Gemini 5u C18(2) 110A, AXI. 50×30.00 mm 5 micron: 7.3-minute run, 47 mL/min, 40% ACN/H2O, 0.1% NH4OH to 90% ACN/H2O, 0.1% NH4OH with UV detection at 254 nm)

Sources & evidence

ORD record
ord-84549fe95b914557b1362ccba6ef7dd5
Source dataset
uspto-grants-2016_09
Patent number
US09446034B2

Linked notes

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