Cesium carbonate → HCID 89525989, compound

HRID 920258Notes

Reaction equation

HRID 920258 reaction equation
Br[C:2]1[CH:3]=[C:4]([C@H:8]([N:10]2[C:14]3[CH:15]=[C:16]([F:28])[C:17]([S:19]([NH:22][C:23]4[S:27][N:26]=[CH:25][N:24]=4)(=[O:21])=[O:20])=[CH:18][C:13]=3[O:12][C:11]2=[O:29])[CH3:9])[CH:5]=[CH:6][CH:7]=1.[CH3:30][N:31]1[CH:35]=[CH:34][C:33](B2OC(C)(C)C(C)(C)O2)=[N:32]1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[F:28][C:16]1[C:17]([S:19]([NH:22][C:23]2[S:27][N:26]=[CH:25][N:24]=2)(=[O:21])=[O:20])=[CH:18][C:13]2[O:12][C:11](=[O:29])[N:10]([C@@H:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([C:33]4[CH:34]=[CH:35][N:31]([CH3:30])[N:32]=4)[CH:3]=3)[CH3:9])[C:14]=2[CH:15]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 27600771-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 89533766HCID 89533766, compound

Product 1

HCID 89525989HCID 89525989, compound

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
90 °C

Procedure

In a sealed vial, compound of Formula 28-2 (45 mg, 0.090 mmol), 1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (21 mg, 0.10 mmol), PdCl2(dppf)-CH2Cl2 adduct (7.3 mg, 0.009 mmol), and cesium carbonate (88 mg, 0.270 mmol) were combined in dioxane (1 mL) and water (0.14 mL). The mixture was heated at 90° C. for 24 hours. The mixture was diluted with dioxane (4 mL), filtered through a celite pad, and the filtrate was concentrated. The resulting residue was purified by reverse phase HPLC (20-100% MeCN in water with 0.1% TFA, C18 column) to yield 28-3 as a white solid. 1H NMR δ (ppm)(DMSO-d): 8.50 (s, 1H); 7.74 (d, J=5.6 Hz, 1H); 7.63 (s, 1H); 7.52-7.46 (m, 5H); 7.41 (d, J=9.8 Hz, 1H); 6.40 (d, J=1.9 Hz, 1H); 5.65 (q, J=7.2 Hz, 1H); 3.79 (s, 3H); 1.91 (d, J=7.2 Hz, 3H). LRMS C21H18FN604S2 [M+H] calc 501.08, obs 501.0.

Workup

  1. filtrationfiltered through a celite pad
  2. concentrationthe filtrate was concentrated
  3. customThe resulting residue was purified by reverse phase HPLC (20-100% MeCN in water with 0.1% TFA, C18 column)

Sources & evidence

ORD record
ord-4b319dfc1658461ba47ce70dbfb41fb1
Source dataset
uspto-grants-2016_03
Patent number
US09273040B2

Reaction notes

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