Dichloromethane → HCID 86715488, compound

HRID 2284579Notes

Reaction equation

HRID 2284579 reaction equation
Cl[C:2]1[C:3]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([CH3:14])[CH:9]=2)=[N:4][CH:5]=[CH:6][CH:7]=1.[CH3:15][N:16]1[C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=2[N:18]=[C:17]1B(O)O.C(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+]>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].O1CCOCC1>[CH3:15][N:16]1[C:20]2[CH:21]=[C:22]([C:2]3[C:3]([C:8]4[CH:9]=[C:10]([CH3:14])[CH:11]=[CH:12][CH:13]=4)=[N:4][CH:5]=[CH:6][CH:7]=3)[CH:23]=[CH:24][C:19]=2[N:18]=[CH:17]1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 49964158HCID 49964158, compoundHCID 86715487HCID 86715487, compound

Product 1

HCID 86715488HCID 86715488, compound

Reagents, catalysts & solvents 2

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

Conditions

Temperature
150 °C

Procedure

1,4-Dioxane (3 mL) was transferred to a microwave vial (Smith Creator®) containing 3-chloro-2-(3-methylphenyl)pyridine (100 mg, 0.49 mmol), 1-methyl-1H-benzimidazole boronic acid (95 mg, 0.54 mmol), PdCl2(dppf)2.CH2Cl2 (35 mg, 0.042 mmol) and 2M aq. Na2CO3 (0.6 mL, 1.2 mmol). Slow stream of argon was bubbled through the heterogeneous red solution while stirring the reaction mixture. The vial was capped and heated in a microwave at 150° C. for 50 min. Progress of the reaction was analyzed by LC/MS. The reaction mixture was passed through a pad of Celite® and washed the pad with EtOAc (10 mL). The filtrate was concentrated and purified by preparative HPLC. Subsequently, product fractions were concentrated, diluted with water, neutralized with aq. NaHCO3 and extracted with EtOAc. Organic layer was dried over anhydrous Na2SO4, filtered and concentrated. The concentrate was dissolved in acetonitrile/water (1:1, 15 mL) and allowed to freeze by external cooling in dry ice/acetone. Lyophilization of the frozen residue resulted in an off-white solid of 1-methyl-6-(2-m-tolylpyridin-3-yl)-1H-benzo[d]imidazole. 1H NMR (DMSO-d6): δ 8.64 (dd, 1H, J=1.7 and 4.7 Hz), 8.16 (s, 1H), 7.87 (dd, 1H, J=1.7 and 7.6 Hz), 7.51 (d, 1H, J=1.5 Hz), 7.47-7.43 (m, 2H), 7.27 (s, 1H), 7.03-6.97 (m, 2H), 6.90 (app d, 1H, J=6.7 Hz), 6.85 (dd, 1H, J=8.5 Hz), 3.76 (s, 3H), 2.19 (s, 3H). 19F NMR (DMSO-d6): δ −114.29 (s).LCMS: rt 3.16 min (A), purity 97%, MS (m/e) 300 (MH

Workup

  1. customwas bubbled through the heterogeneous red solution
  2. customThe vial was capped
  3. washwashed the pad with EtOAc (10 mL)
  4. concentrationThe filtrate was concentrated
  5. custompurified by preparative HPLC
  6. concentrationSubsequently, product fractions were concentrated
  7. additiondiluted with water
  8. extractionextracted with EtOAc
  9. dry with materialOrganic layer was dried over anhydrous Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. dissolutionThe concentrate was dissolved in acetonitrile/water (1:1, 15 mL)
  13. temperatureby external cooling in dry ice/acetone

Sources & evidence

ORD record
ord-31db8f6d04eb4dfca6c2217282c650dc
Source dataset
uspto-grants-2015_09
Patent number
US09145433B2

Reaction notes

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