Cesium carbonate → HCID 57635865, compound

HRID 2109942Notes

Reaction equation

HRID 2109942 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:12]([NH2:13])=[CH:11][C:10]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)=[N:9]1.Cl[C:22]1[N:32]=[CH:31][CH:30]=[CH:29][C:23]=1[C:24]([O:26][CH2:27][CH3:28])=[O:25].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-])=O.[Cs+].[Cs+]>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]>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:12]([NH:13][C:22]2[N:32]=[CH:31][CH:30]=[CH:29][C:23]=2[C:24]([O:26][CH2:27][CH3:28])=[O:25])=[CH:11][C:10]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)=[N:9]1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 2796614Ethyl chloronicotinateHCID 43381573HCID 43381573, compound

Product 1

HCID 57635865HCID 57635865, compoundYield 90.2%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
110 °C

Procedure

To a dried 15 mL tube was added 1-(2-chlorophenyl)-3-(4-fluorophenyl)-1H-pyrazol-5-amine (300 mg, 1.04 mmol), synthesized in the same manner as intermediate G, ethyl 2-chloronicotinate (194 mg, 1.04 mmol), Pd2(dba)3 (48 mg, 0.05 mmol), BINAP (65 mg, 0.10 mmol), and Cs2CO3 (679 mg, 2.09 mmol). The flask was degassed followed by addition of toluene (4 mL) and the mixture was then heated to 110° C. for 20 h. The mixture was cooled to rt, filtered through a silica gel plug using ethyl acetate as eluent, concentrated to dryness, and subjected to HPLC purification using a gradient elution from 45% to 90% acetonitrile in water to afford 410 mg (90%) of the desired product. 1H NMR (300 MHz, CD2Cl2) δ 10.17 (s, 1H), 8.46 (dd, 1H), 8.22 (dd, 1H), 7.89 (dd, 2H), 7.48-7.64 (m, 4H), 7.23 (s, 1H), 7.12 (t, 2H), 7.84 (dd, 1H), 4.24 (q, 2H), 1.32 (t, 3H); ES-MS m/z 437.2 (MH+); HPLC RT (min) 4.38.

Workup

  1. customThe flask was degassed
  2. additionfollowed by addition of toluene (4 mL)
  3. temperatureThe mixture was cooled to rt
  4. filtrationfiltered through a silica gel plug
  5. concentrationconcentrated to dryness
  6. customsubjected to HPLC purification
  7. washa gradient elution from 45% to 90% acetonitrile in water

Sources & evidence

ORD record
ord-9f1b2f00015b4e30a21984d3a02a37df
Source dataset
uspto-grants-2009_04
Patent number
US07517878B2

Reaction notes

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