Cesium carbonate → HCID 59233815, compound

HRID 2068410Notes

Reaction equation

HRID 2068410 reaction equation
FC(F)(F)S(O[C:7]1[C:12]([N:13]([CH2:18][CH3:19])[S:14]([CH3:17])(=[O:16])=[O:15])=[CH:11][N:10]2[N:20]=[C:21]([C:27]3[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=3)[C:22]([C:23](=[O:26])[NH:24][CH3:25])=[C:9]2[CH:8]=1)(=O)=O.[CH3:36][C:37]1[CH:54]=[CH:53][C:40]([C:41]([NH:43][C:44]2([C:47]3[CH:52]=[CH:51][CH:50]=[CH:49][N:48]=3)[CH2:46][CH2:45]2)=[O:42])=[CH:39][C:38]=1B1OC(C)(C)C(C)(C)O1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O>[CH2:18]([N:13]([C:12]1[C:7]([C:38]2[CH:39]=[C:40]([C:41](=[O:42])[NH:43][C:44]3([C:47]4[CH:52]=[CH:51][CH:50]=[CH:49][N:48]=4)[CH2:45][CH2:46]3)[CH:53]=[CH:54][C:37]=2[CH3:36])=[CH:8][C:9]2[N:10]([N:20]=[C:21]([C:27]3[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=3)[C:22]=2[C:23]([NH:24][CH3:25])=[O:26])[CH:11]=1)[S:14]([CH3:17])(=[O:15])=[O:16])[CH3:19]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 672178374-methyl-N-(1-(pyridin-2-yl)cyclopropyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamideHCID 86639963HCID 86639963, compound

Product 1

HCID 59233815HCID 59233815, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

6-(N-ethylmethylsulfonamido)-2-(4-fluorophenyl)-3-(methylcarbamoyl)pyrazolo[1,5-a]pyridin-5-yl trifluoromethanesulfonate (0.07 g, 0.13 mmol, 1 eq), 4-methyl-N-(1-(pyridin-2-yl)cyclopropyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (0.054 g, 0.14 mmol, 1.1 eq), tetrakistriphenylphosphine palladium (0.0045 g, 0.0039 mmol, 0.03 eq) and cesium carbonate (0.12 g, 0.39 mmol, 3 eq) were dissolved in 1,4-dioxane (10 ml) and water (2 ml). Nitrogen gas was passed through the solution and the reaction was heated at 90° C. for 14 h. The solution was filtered through celite. Water was added to the filtrate which was then extracted with ethyl acetate. The organic layer was concentrated and the residue obtained purified by Preparative HPLC. Yield: 22 mg (26%). 1HNMR (400 MHz, CD3OD): δ 1.12 (broad s, 3H), 1.35 (s, 2H), 1.66 (s, 2H), 2.34 (s, 3H), 2.85 (s, 3H), 3.00-3.32 (br, 3H), 3.51 (br, 2H), 7.13 (m, 1H), 7.24 (m, 2H), 7.46 (m, 2H), 7.68 (m, 1H), 7.97 (m, 4H), 8.0 (s, 1H), 8.41-8.42 (d, J=4 Hz, 1H), 8.92 (s, 1H). LCMS: (ES+) m/z=641.2 (M+H) Method: Column-Ascentis Express C18 (5×2.1 mm-2.7 μm); Mphase A: 2% MeCN-98% H2O-10 mM NH4COOH; Mphase B: 98% MeCN-2% H2O-10 mM NH4COOH Flow: 1 mL/Min; RT min: 1.796; Wavelength: 220 nm. HPLC Method: SUNFIRE C18 (4.6×150) mm, 3.5 micron; Buffer: 0.05% TFA in water pH 2.5; Mobile Phase A: Buffer: MeCN (95:5); Mobile Phase B: MeCN: Buffer (95:5); FLOW: 1 ml/min; Wavelength: 254 nm, RT min: 8.675; Purity: 96.6%.

Workup

  1. filtrationThe solution was filtered through celite
  2. additionWater was added to the filtrate which
  3. extractionwas then extracted with ethyl acetate
  4. concentrationThe organic layer was concentrated
  5. customthe residue obtained
  6. custompurified by Preparative HPLC
  7. customRT min
  8. custom254 nm, RT min

Sources & evidence

ORD record
ord-61b8084a62ab412396f46d823e64c69f
Source dataset
uspto-grants-2012_10
Patent number
US08293909B2

Reaction notes

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