Potassium Acetate → HCID 58541883, compound

HRID 1966697Notes

Reaction equation

HRID 1966697 reaction equation
[NH2:1][C:2]1[C:7]([CH2:8][OH:9])=[CH:6][C:5](Br)=[CH:4][N:3]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.CC([O-])=O.[K+].Br[C:35]1[CH:60]=[CH:59][C:38]2[N:39]([C:55]([CH3:58])([CH3:57])[CH3:56])[C:40]([C:42]3[CH:47]=[C:46]([O:48][CH3:49])[CH:45]=[CH:44][C:43]=3[N:50]3[CH:54]=[CH:53][CH:52]=[N:51]3)=[N:41][C:37]=2[CH:36]=1>O1CCOCC1.CN(C=O)C.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>[NH2:1][C:2]1[C:7]([CH2:8][OH:9])=[CH:6][C:5]([C:35]2[CH:60]=[CH:59][C:38]3[N:39]([C:55]([CH3:56])([CH3:58])[CH3:57])[C:40]([C:42]4[CH:47]=[C:46]([O:48][CH3:49])[CH:45]=[CH:44][C:43]=4[N:50]4[CH:54]=[CH:53][CH:52]=[N:51]4)=[N:41][C:37]=3[CH:36]=2)=[CH:4][N:3]=1

Participants

10

Reactant 4

HCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 108913662-Amino-5-bromo-3-(hydroxymethyl)pyridineHCID 58541942HCID 58541942, compound

Product 1

HCID 58541883HCID 58541883, compoundYield 7.3%

Reagents, catalysts & solvents 5

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst2×HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 10340Sodium CarbonateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a high pressure vessel are added 2-amino-3-hyroxymethyl-5-bromopyridine (90 mg, 0.44 mmol), bis(pinacolato)diboron (135 mg, 0.53 mmol) and KOAc (131 mg, 1.33 mmol) in 10 mL of 1,4-dioxane. The solution is degassed with nitrogen for 10 minutes, followed by the addition of PdCl2(dppf) (36 mg, 0.04 mmol). The reaction mixture is warmed to 80° C. and stirred for 1 hour. After this time a solution of 5-bromo-1-tert-butyl-2-(5-methoxy-2-pyrazol-1-yl-phenyl)-1H-benzimidazole (226 mg, 0.53 mmol) and additional PdCl2(dppf) (16 mg, 0.02 mmol) in DMF (1 mL) and 2M Na2CO3 (0.1 mL) are added. The reaction is heated at 80° C. for 12 hours, then cooled to room temperature and poured into water. The mixture is extracted with EtOAc (3×) and the combined organics are dried (MgSO4), filtered and concentrated. Purification via flash chromatography (12 g silica gel, 0-8% MeOH/CH2Cl2) and preparative TLC (0.5 mm silica gel, 8% MeOH/CH2Cl2) gives the title compound (15 mg, 7%). LCMS (ESMS): m/z 469.20 (M++1)

Workup

  1. customThe solution is degassed with nitrogen for 10 minutes
  2. temperatureThe reaction is heated at 80° C. for 12 hours
  3. temperaturecooled to room temperature
  4. extractionThe mixture is extracted with EtOAc (3×)
  5. dry with materialthe combined organics are dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification via flash chromatography (12 g silica gel, 0-8% MeOH/CH2Cl2) and preparative TLC (0.5 mm silica gel, 8% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-ceb40cc8fbd848869c721eadb74924eb
Source dataset
uspto-grants-2013_04
Patent number
US08420655B2

Reaction notes

Loading…