Dichloromethane → HCID 45376884, compound

HRID 2195744Notes

Reaction equation

HRID 2195744 reaction equation
C(OC([N:8]1[C:12]2[CH:13]=[CH:14][C:15](Br)=[CH:16][C:11]=2[N:10]=[C:9]1[CH2:18][C:19]1[CH:24]=[CH:23][N:22]=[CH:21][CH:20]=1)=O)(C)(C)C.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.CC([O-])=O.[K+].ClCCl.[CH:51]1([C@H:57]([NH:62][C:63]([C:65]2[O:66][C:67](Br)=[CH:68][CH:69]=2)=[O:64])[C:58](=[O:61])[NH:59][CH3:60])[CH2:56][CH2:55][CH2:54][CH2:53][CH2:52]1.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].O>[CH:51]1([C@H:57]([NH:62][C:63]([C:65]2[O:66][C:67]([C:15]3[CH:14]=[CH:13][C:12]4[N:8]=[C:9]([CH2:18][C:19]5[CH:20]=[CH:21][N:22]=[CH:23][CH:24]=5)[NH:10][C:11]=4[CH:16]=3)=[CH:68][CH:69]=2)=[O:64])[C:58](=[O:61])[NH:59][CH3:60])[CH2:56][CH2:55][CH2:54][CH2:53][CH2:52]1

Participants

9

Reactant 6

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 58492140HCID 58492140, compoundHCID 58505545HCID 58505545, compound

Product 1

HCID 45376884HCID 45376884, compound

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

A pressure vial is charged with 5-bromo-2-pyridin-4-ylmethyl-1H-benzimidazole-1-carboxylic acid tert-butyl ester (100 mg, 0.26 mmol), bis(pinacolato)diboron (72 mg, 0.28 mmol), KOAc (99 mg, 1.01 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (1:1) (PdCl2(dppf)*CH2Cl2) (8.2 mg, 0.01 mmol). After flushing with nitrogen, DME (2 mL) is added and the reaction stirred at 100° C. for 2 h. The mixture is cooled to room temperature before 5-bromo-furan-2-carboxylic acid ((S)-cyclohexyl-methylcarbamoyl-methyl)-amide (88 mg, 0.26 mmol), PdCl2(dppf)*CH2Cl2 (8.2 mg, 0.01 mmol), and 2M Na2CO3 solution (0.84 mL, 1.68 mmol) are added. The mixture is stirred at 110° C. for 8 h. Water is added and the mixture is extracted with EtOAc. The organic layer was washed with brine and dried over MgSO4. After removal of the solvent, the residue was purified by reversed phase (HPLC). The product is obtained as a pale yellow solid. 19 mg, 15%, LC/MS ESI m/z (M+H)+=472.46

Workup

  1. customAfter flushing with nitrogen, DME (2 mL)
  2. additionis added
  3. additionare added
  4. stirringThe mixture is stirred at 110° C. for 8 h
  5. extractionthe mixture is extracted with EtOAc
  6. washThe organic layer was washed with brine
  7. dry with materialdried over MgSO4
  8. customAfter removal of the solvent
  9. customthe residue was purified by reversed phase (HPLC)
  10. customThe product is obtained as a pale yellow solid

Sources & evidence

ORD record
ord-6f245a23eba541a8b59b0ef5c180adcb
Source dataset
uspto-grants-2012_12
Patent number
US08338367B2

Reaction notes

Loading…