Potassium Acetate → HCID 131732547, compound

HRID 872060Notes

Reaction equation

HRID 872060 reaction equation
Br[C:2]1[C:3]([O:12][CH2:13][C@H:14]2[CH2:16][C@@H:15]2[C:17]2[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][N:18]=2)=[N:4][C:5]2[C:10]([CH:11]=1)=[N:9][CH:8]=[CH:7][CH:6]=2.[B:25]1(B2OC(C)(C)C(C)(C)O2)[O:29]C(C)(C)C(C)(C)[O:26]1.C([O-])(=O)C.[K+]>O1CCOCC1.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]>[CH3:24][O:23][C:20]1[CH:21]=[CH:22][C:17]([C@H:15]2[CH2:16][C@@H:14]2[CH2:13][O:12][C:3]2[C:2]([B:25]([OH:29])[OH:26])=[CH:11][C:10]3[C:5](=[CH:6][CH:7]=[CH:8][N:9]=3)[N:4]=2)=[N:18][CH:19]=1

Participants

6

Reactant 3

HCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 1176891283-bromo-2-{[(1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl]-methoxy}-1,5-naphthyridine

Product 1

HCID 131732547HCID 131732547, compound

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

A mixture of 3-bromo-2-{[(1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl]-methoxy}-1,5-naphthyridine (LL2) (800 mg, 2.1 mmol), bis(pinacolato)diboron (789 mg, 3.1 mmol), potassium acetate (813 mg, 8.3 mmol) and PdCl2(dppf) (303 mg, 0.41 mmol) in dioxane (10.4 mL) under N2 was heated at 100° C. for 14 hours. The reaction mixture was cooled to ambient temperature, partitioned between EtOAc (125 mL) and sat. sodium bicarbonate (25 mL), washed with water (25 mL), dried over MgSO4, filtered and concentrated. The resulting residue was purified by flash chromatography (20% to 100% EtOAc in hexanes; hydrolysis on silica gel to boronic acid led to elution with 9:1 chloroform/methanol) to afford the title compound as a brown foam. LRMS m/z (M+H) 352.1 found, 352.1 required.

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. custompartitioned between EtOAc (125 mL) and sat. sodium bicarbonate (25 mL)
  3. washwashed with water (25 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe resulting residue was purified by flash chromatography (20% to 100% EtOAc in hexanes; hydrolysis on silica gel to boronic acid led to elution with 9:1 chloroform/methanol)

Sources & evidence

ORD record
ord-b8c8f73074124716bc79400a7f520e31
Source dataset
uspto-grants-2015_03
Patent number
US08975261B2

Reaction notes

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