Potassium Carbonate → HCID 25152788, compound

HRID 2090096Notes

Reaction equation

HRID 2090096 reaction equation
FC(F)(F)S(O[C:7]1[CH2:12][CH2:11][CH:10]([CH2:13][NH:14][C:15](=[O:36])[C:16]2[CH:21]=[CH:20][C:19]([C:22]3[O:23][C:24]4[C:30]([CH:31]([CH3:33])[CH3:32])=[CH:29][C:28]([C:34]#[N:35])=[CH:27][C:25]=4[N:26]=3)=[CH:18][CH:17]=2)[CH2:9][CH:8]=1)(=O)=O.[F:39][C:40]1[CH:45]=[CH:44][C:43](B(O)O)=[CH:42][CH:41]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCCC1.[Pd](Cl)Cl.C(P(C(C)(C)C)[C-]1C=CC=C1)(C)(C)C.[C-]1(P(C(C)(C)C)C(C)(C)C)C=CC=C1.[Fe+2]>[C:34]([C:28]1[CH:29]=[C:30]([CH:31]([CH3:32])[CH3:33])[C:24]2[O:23][C:22]([C:19]3[CH:18]=[CH:17][C:16]([C:15]([NH:14][CH2:13][CH:10]4[CH2:11][CH2:12][C:7]([C:43]5[CH:44]=[CH:45][C:40]([F:39])=[CH:41][CH:42]=5)=[CH:8][CH2:9]4)=[O:36])=[CH:21][CH:20]=3)=[N:26][C:25]=2[CH:27]=1)#[N:35]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 2856454-Fluorophenylboronic acidHCID 59435898HCID 59435898, compound2×

Product 1

HCID 25152788HCID 25152788, compoundYield 83.5%

Reagents, catalysts & solvents 2

HCID 178454861HCID 178454861, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 4-({[4-(5-cyano-7-isopropyl-1,3-benzoxazol-2-yl)benzoyl]amino}methyl)cyclohex-1-en-1-yl trifluoromethanesulfonate (50 mg, 0.091 mmol, INTERMEDIATE 5) and 4-fluorophenyl boronic acid (25 mg, 0.179 mmol) in tetrahydrofuran (2 ml) and 1 M aqueous potassium carbonate (1 ml, 1.000 mmol) was added 1,1′-bis(di-t-butylphosphino)ferrocene palladium dichloride (1 mg, 5.64 μmol). The mixture was microwaved at 100° C. in a sealed tube for 10 min, cooled, and then resubmitted to the reaction conditions for 10 min, at which point LC/MS analysis showed no starting material. The organic phase of the reaction mixture was added directly to a 25 samplet and purified by flash chromatography on a Biotage Horizon, 25M column, eluting with 1 column volume of 100% dichloromethane followed by a gradient of 0 to 100% ethyl acetate in dichloromethane over 10 column volumes, to provide the title compound (37.5 mg, 0.076 mmol, 83% yield). Mass spectrum (ESI) 494.1 (M+1). 1H NMR (500 MHz, CDCl3): δ 8.32 (d, J=8.5 Hz, 2H); 7.96 (d, J=8.0 Hz, 2H), 7.93 (d, J=1.5 Hz, 1H); 7.51 (s, 1H), 7.32 (ddd, J=2.0, 5.5, 8.5 Hz, 2H), 6.99 (t, J=9.0 Hz, 2H), 6.39 (br t, J=5.5 Hz, 1H), 6.03 (s, 1H), 3.42-3.58 (m, 3H), 2.34-2.56 (m, 3H), 1.96-2.08 (m, 3H), 1.46 (d, J=7.0 Hz, 6H), 1.44-1.62 (m, 2H).

Workup

  1. customThe mixture was microwaved at 100° C. in a sealed tube for 10 min
  2. temperaturecooled
  3. customresubmitted to the reaction conditions for 10 min, at which point LC/MS analysis
  4. additionThe organic phase of the reaction mixture was added directly to a 25 samplet
  5. custompurified by flash chromatography on a Biotage Horizon, 25M column
  6. washeluting with 1 column volume of 100% dichloromethane

Sources & evidence

ORD record
ord-68f5c7996d374b6baef2c940824599e4
Source dataset
uspto-grants-2013_05
Patent number
US08436028B2

Reaction notes

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