Cesium carbonate → HCID 25153005, compound

HRID 2090106Notes

Reaction equation

HRID 2090106 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH:37]([CH3:39])[CH3:38])[C:6]2[O:10][C:9]([C:11]3[CH:35]=[CH:34][C:14]([C:15]([NH:17][CH2:18][CH:19]4[CH2:24][CH2:23][C:22](B5OC(C)(C)C(C)(C)O5)=[CH:21][CH2:20]4)=[O:16])=[CH:13][CH:12]=3)=[N:8][C:7]=2[CH:36]=1)#[N:2].Br[C:41]1[CH:46]=[CH:45][C:44]([C:47]([F:50])([F:49])[F:48])=[CH:43][N:42]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCCC1.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].ClCCl>[C:1]([C:3]1[CH:4]=[C:5]([CH:37]([CH3:39])[CH3:38])[C:6]2[O:10][C:9]([C:11]3[CH:35]=[CH:34][C:14]([C:15]([NH:17][CH2:18][CH:19]4[CH2:24][CH2:23][C:22]([C:41]5[CH:46]=[CH:45][C:44]([C:47]([F:50])([F:49])[F:48])=[CH:43][N:42]=5)=[CH:21][CH2:20]4)=[O:16])=[CH:13][CH:12]=3)=[N:8][C:7]=2[CH:36]=1)#[N:2]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 27364342-Bromo-5-(trifluoromethyl)pyridineHCID 59435927HCID 59435927, compound2×

Product 1

HCID 25153005HCID 25153005, compoundYield 48.2%

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 4-(5-cyano-7-isopropyl-1,3-benzoxazol-2-yl)-N-{[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohex-3-en-1-yl]methyl}benzamide (70 mg, 0.133 mmol, INTERMEDIATE 9), 2-bromo-5-(trifluoromethyl)pyridine (45 mg, 0.199 mmol), and cesium carbonate (130 mg, 0.400 mmol) in tetrahydrofuran (6 ml) and water (0.6 ml) was added dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II)-dichloromethane adduct (7 mg, 8.57 mmol). The mixture was heated to reflux and stirred at this temperature overnight. The reaction mixture was cooled and added directly to a 25 samplet, and then purified by flash chromatography on a Biotage Horizon, 25S 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 (35 mg, 0.064 mmol, 48.2% yield). Mass spectrum (ESI) 545.1 (M+1). 1H NMR (500 MHz, CDCl3): δ 8.80 (s, 1H), 8.34 (d, J=8.5 Hz, 2H); 7.97 (d, J=8.5 Hz, 2H), 7.94 (d, J=1.0 Hz, 1H); 7.85 (d, J=8.0 Hz, 1H), 7.52 (s, 1H), 7.48 (d, J=8.5 Hz, 1H), 6.83, (br s, 1H), 6.37 (br t, J=5.5 Hz, 1H), 3.54 (br t, J=4.5 Hz, 2H), 3.48 (septet, J=6.5 Hz, 1H), 2.75 (br d, J=16.5 Hz, 1H), 2.53 (br d, J=15.5 Hz, 2H), 2.04-2.16 (m, 3H), 1.50-1.68 (m, 3H), 1.46 (d, J=7.0 Hz, 6H), 1.25 (m, 2H).

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux
  3. temperatureThe reaction mixture was cooled
  4. additionadded directly to a 25 samplet
  5. custompurified by flash chromatography on a Biotage Horizon, 25S column
  6. washeluting with 1 column volume of 100% dichloromethane

Sources & evidence

ORD record
ord-bfb9bc300cf94e56827b6744f811c216
Source dataset
uspto-grants-2013_05
Patent number
US08436028B2

Reaction notes

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