Cesium carbonate → HCID 90416024, compound

HRID 1428551Notes

Reaction equation

HRID 1428551 reaction equation
[CH2:1]([O:3][C:4]1[C:5]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=2)=[N:6][CH:7]=[C:8](B2OC(C)(C)C(C)(C)O2)[CH:9]=1)[CH3:2].[C:29]([C:32]1[N:37]=[CH:36][C:35]([NH:38][C:39](=[O:49])[CH2:40][C:41]2[CH:46]=[CH:45][C:44](Br)=[CH:43][C:42]=2[F:48])=[CH:34][C:33]=1[C:50]([F:53])([F:52])[F:51])(=[O:31])[CH3:30].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:29]([C:32]1[N:37]=[CH:36][C:35]([NH:38][C:39](=[O:49])[CH2:40][C:41]2[CH:46]=[CH:45][C:44]([C:8]3[CH:7]=[N:6][C:5]([O:19][CH2:20][C:21]4[CH:22]=[CH:23][C:24]([O:27][CH3:28])=[CH:25][CH:26]=4)=[C:4]([O:3][CH2:1][CH3:2])[CH:9]=3)=[CH:43][C:42]=2[F:48])=[CH:34][C:33]=1[C:50]([F:51])([F:53])[F:52])(=[O:31])[CH3:30]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 904167753-Ethoxy-2-((4-methoxybenzyl)oxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 90416863HCID 90416863, compound

Product 1

HCID 90416024HCID 90416024, compoundYield 38.7%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

To a mixture of 3-ethoxy-2-((4-methoxybenzyl)oxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (100 mg, 0.260 mmol) in 1,4-dioxane (3 mL) and H2O (1 mL) was added N-(6-acetyl-5-(trifluoromethyl)pyridin-3-yl)-2-(4-bromo-2-fluorophenyl)acetamide (120 mg, 0.286 mmol), cesium carbonate (169 mg, 0.519 mmol) and PdCl2(dppf) (18.99 mg, 0.026 mmol). The mixture was stirred under a N2 atmosphere at 110° C. for 30 min under microwave. Then the reaction residue was filtered and the filtrate was concentrated to give the crude product, which was purified by preparative TLC (PE/EA=1:1, Rf=0.6) to yield a light yellow solid of N-(6-acetyl-5-(trifluoromethyl)pyridin-3-yl)-2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)acetamide (100 mg, 0.100 mmol, 38.7% yield): 1H NMR (400 MHz, CD3OD) δ 9.02 (s, 1H), 8.62 (s, 1H), 8.13 (d, J=2.0 Hz, 2H), 7.42 (d, J=9.0 Hz, 4H), 7.33 (d, J=2.5 Hz, 2H), 6.94 (s, 1H), 5.39 (s, 2H), 4.15-4.09 (m, 2H), 3.91 (s, 2H), 2.03 (s, 3H), 1.26 (t, J=7.0 Hz, 3H); ES-LCMS m/z 598.1 (M+H).

Workup

  1. filtrationThen the reaction residue was filtered
  2. concentrationthe filtrate was concentrated
  3. customto give the crude product, which
  4. customwas purified by preparative TLC (PE/EA=1:1, Rf=0.6)

Sources & evidence

ORD record
ord-f574a1199bb8429987006f403f55fd90
Source dataset
uspto-grants-2015_01
Patent number
US08937071B2

Reaction notes

Loading…