Sodium Carbonate → HCID 117667664, compound

HRID 712692Notes

Reaction equation

HRID 712692 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[N:10][CH:11]=1)[N:8]([C:12]([NH2:14])=[O:13])[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:39]1[CH:40]=[C:41]([C:45]2([OH:49])[CH2:48][O:47][CH2:46]2)[CH:42]=[N:43][CH:44]=1.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]>[OH:49][C:45]1([C:41]2[CH:40]=[C:39]([C:2]3[CH:3]=[C:4]4[C:9](=[N:10][CH:11]=3)[N:8]([C:12]([NH2:14])=[O:13])[CH2:7][CH2:6][CH2:5]4)[CH:44]=[N:43][CH:42]=2)[CH2:48][O:47][CH2:46]1

Participants

8

Reactant 5

HCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 754066851432621-15-2HCID 117667602HCID 117667602, compound

Product 1

HCID 117667664HCID 117667664, compoundYield 6.3%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst2×HCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
80 °C

Procedure

A vial containing 6-bromo-3,4-dihydro-2H-[1,8]naphthyridine-1-carboxylic acid amide (350 mg, 1.4 mmol), bis(pinacolato)diboron (573 mg, 2.3 mmol), 1,1′-bis(diphenylphosphino)ferrocenedichloropalladium (II) (50 mg, 0.068 mmol) and potassium acetate (604 mg, 6.2 mmol) in 1,4-dioxane (10 mL) is flushed with Ar, sealed tightly and heated to 80° C. for 2 h. The reaction mixture is cooled to room temperature and a solution of 3-(5-bromo-pyridin-3-yl)-oxetan-3-ol (314 mg, 1.37 mmol) in 1,4-dioxane (4 mL), aqueous sodium carbonate solution (2M, 1.4 mL, 2.7 mmol) and additional 1,1′-bis(diphenylphosphino)ferrocenedichloropalladium (II) (50 mg, 0.068 mmol) are added. The mixture is flushed with Ar, sealed tightly and heated to 100° C. for 90 min. After cooling to room temperature the mixture is partitioned between water and EtOAc. The layers are separated and the aqueous is further extracted with EtOAc. The combined organic layers are washed with brine, dried (Na2SO4) and concentrated. To the residue is added MeOH to form a precipitate which is collected by filtration to afford the title compound (28 mg).

Workup

  1. customis flushed with Ar
  2. customsealed tightly
  3. temperatureThe reaction mixture is cooled to room temperature
  4. customThe mixture is flushed with Ar
  5. customsealed tightly
  6. temperatureheated to 100° C. for 90 min
  7. temperatureAfter cooling to room temperature the mixture
  8. customis partitioned between water and EtOAc
  9. customThe layers are separated
  10. extractionthe aqueous is further extracted with EtOAc
  11. washThe combined organic layers are washed with brine
  12. dry with materialdried (Na2SO4)
  13. concentrationconcentrated
  14. additionTo the residue is added MeOH
  15. customto form a precipitate which
  16. filtrationis collected by filtration

Sources & evidence

ORD record
ord-2fc45fcae2334ecd9384057d737bd04c
Source dataset
uspto-grants-2015_11
Patent number
US09181272B2

Reaction notes

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