Sodium Carbonate → HCID 117667280, compound

HRID 712724Notes

Reaction equation

HRID 712724 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[N:10][CH:11]=1)[NH:8][CH2:7][CH2:6][CH2:5]2.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].Br[C:36]1[CH:37]=[N:38][CH:39]=[C:40]([F:46])[C:41]=1[C:42]([OH:45])([CH3:44])[CH3:43].C([O-])([O-])=O.[Na+].[Na+]>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]>[F:46][C:40]1[CH:39]=[N:38][CH:37]=[C:36]([C:2]2[CH:11]=[N:10][C:9]3[NH:8][CH2:7][CH2:6][CH2:5][C:4]=3[CH:3]=2)[C:41]=1[C:42]([OH:45])([CH3:43])[CH3:44]

Participants

8

Reactant 5

HCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 179301266-Bromo-1,2,3,4-tetrahydro-1,8-naphthyridineHCID 67155071HCID 67155071, compound

Product 1

HCID 117667280HCID 117667280, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

To a vial is added 6-bromo-1,2,3,4-tetrahydro-[1,8]naphthyridine, Intermediate A (144 mg, 0.68 mmol), bis(pinacolato)diboron (223 mg, 0.88 mmol), potassium acetate (200 mg, 2 mmol) and [1,1′-bis(diphenylphosphino)ferrocene)dichloropalladium(II) (50 mg, 0.07 mmol) in 5 ml of 1,4-dioxane. The reaction mixture is stirred at 120° C. under Ar for 2 hours. The reaction mixture is cooled down to room temperature, followed by the addition of 2-(3-bromo-5-fluoro-pyridin-4-yl)-propan-2-ol (190 mg, 0.81 mmol), 2M Na2CO3 (0.67 ml, 1.35 mmol) and [1,1′-bis(diphenylphosphino)ferrocene)dichloropalladium(II) (25 mg, 0.034 mmol). The reaction mixture is stirred under Ar at 120° C. for 3 hours. The reaction mixture is concentrated. The residue is diluted with EtOAc, washed with water, brine, dried over anhydrous Na2SO4, filtered and concentrated to give the crude product. Purification by the flash column chromatography affords 72 mg of 2-[3-fluoro-5-(5,6,7,8-tetrahydro-[1,8]naphthyridin-3-yl)-pyridin-4-yl]-propan-2-ol.

Workup

  1. temperatureThe reaction mixture is cooled down to room temperature
  2. stirringThe reaction mixture is stirred under Ar at 120° C. for 3 hours
  3. concentrationThe reaction mixture is concentrated
  4. additionThe residue is diluted with EtOAc
  5. washwashed with water, brine
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give the crude product
  10. customPurification by the flash column chromatography

Sources & evidence

ORD record
ord-35f32584132b4e9099f800c59c453418
Source dataset
uspto-grants-2015_11
Patent number
US09181272B2

Reaction notes

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