Sodium Carbonate → HCID 117667637、化合物

HRID 712689ノート

反応式

HRID 712689 の反応式
Br[C:2]1[CH:3]=[C:4]([C:8](=[O:10])[CH3:9])[CH:5]=[N:6][CH:7]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].[C:34]([O:38][C:39]([N:41]1[C:50]2[C:45](=[CH:46][C:47](Br)=[CH:48][N:49]=2)[CH2:44][CH2:43][CH2:42]1)=[O:40])([CH3:37])([CH3:36])[CH3:35].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]>[C:34]([O:38][C:39]([N:41]1[C:50]2[C:45](=[CH:46][C:47]([C:2]3[CH:7]=[N:6][CH:5]=[C:4]([C:8](=[O:10])[CH3:9])[CH:3]=3)=[CH:48][N:49]=2)[CH2:44][CH2:43][CH2:42]1)=[O:40])([CH3:37])([CH3:35])[CH3:36]

参加物

8

反応物 5

HCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 8204233-Acetyl-5-bromopyridineHCID 2733548Bis(pinacolato)diboraneHCID 11833959tert-Butyl 6-bromo-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylate

生成物 1

HCID 117667637HCID 117667637、化合物収率 79.3%

試薬・触媒・溶媒 2

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

反応条件

温度
70 °C

実験手順

A vial containing 1-(5-bromo-pyridin-3-yl)-ethanone (1.59 g, 8.0 mmol), bis(pinacolato)diboron (2.53 g, 9.9 mmol), 1,1′-bis(diphenylphosphino)ferrocenedichloropalladium(II) DCM complex (486 mg, 0.66 mmol) and potassium acetate (1.96 g, 19.9 mmol) in 1,4-dioxane (100 mL) is flushed with Ar, sealed tightly and heated to 70° C. for 16 h. The reaction mixture is cooled to room temperature and 6-bromo-3,4-dihydro-2H-[1,8]naphthyridine-1-carboxylic acid tert-butyl ester (2.08 g, 6.6 mmol), aqueous sodium carbonate solution (2M, 9.9 mL, 19.9 mmol) and additional 1,1′-bis(diphenylphosphino)ferrocenedichloropalladium (II) (486 mg, 0.66 mmol) are added. The mixture is flushed with Ar, sealed tightly and heated to 100° C. for 2 h. The reaction mixture is cooled to room temperature and 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 and filtered through diatomaceous earth, rinsing well with EtOAc. The filtrate is dried (Na2SO4) and concentrated. The crude product is purified by silica gel column (25-100% EtOAc in heptane) to afford 6-(5-acetyl-pyridin-3-yl)-3,4-dihydro-2H-[1,8]naphthyridine-1-carboxylic acid tert-butyl ester (1.85 g).

後処理

  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 2 h
  7. temperatureThe reaction mixture is cooled to room temperature
  8. custompartitioned 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. filtrationfiltered through diatomaceous earth
  13. washrinsing well with EtOAc
  14. dry with materialThe filtrate is dried (Na2SO4)
  15. concentrationconcentrated
  16. customThe crude product is purified by silica gel column (25-100% EtOAc in heptane)

出典と根拠

ORDレコード
ord-edf43368b2a14681b669d04a058c6e5d
出典データセット
uspto-grants-2015_11
特許番号
US09181272B2

反応ノート

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