Ethyl Acetate → 6-(5-Dimethylcarbamoylmethyl-pyridin-3-yl)-3,4-dihydro-2H-[1,8]naphthyridine-1-carboxylic acid amide

HRID 712652Notes

Reaction equation

HRID 712652 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH2:8][C:9]([N:11]([CH3:13])[CH3:12])=[O:10])[CH:5]=[N:6][CH:7]=1.C([O-])([O-])=O.[Na+].[Na+].O1CCOCC1.CC1(C)C(C)(C)OB([C:34]2[CH:35]=[C:36]3[C:41](=[N:42][CH:43]=2)[N:40]([C:44]([NH2:46])=[O:45])[CH2:39][CH2:38][CH2:37]3)O1.CCOC(C)=O>O>[CH3:12][N:11]([CH3:13])[C:9]([CH2:8][C:4]1[CH:3]=[C:2]([C:34]2[CH:35]=[C:36]3[C:41](=[N:42][CH:43]=2)[N:40]([C:44]([NH2:46])=[O:45])[CH2:39][CH2:38][CH2:37]3)[CH:7]=[N:6][CH:5]=1)=[O:10]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 537850792-(5-bromopyridin-3-yl)-N,N-dimethylacetamideHCID 1317339886-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,4-dihydro-2H-[1,8]naphthyridine-1-carboxylic acid amide 1,4-dioxane

Product 1

HCID 1176669916-(5-Dimethylcarbamoylmethyl-pyridin-3-yl)-3,4-dihydro-2H-[1,8]naphthyridine-1-carboxylic acid amideYield 7.9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

2-(5-Bromo-pyridin-3-yl)-N,N-dimethyl-acetamide (73 mg, 0.30 mmol) and 2.0 M Na2CO3 aqueous solution (0.30 mL, 0.60 mmol) are added into the crude 6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,4-dihydro-2H-[1,8]naphthyridine-1-carboxylic acid amide 1,4-dioxane solution (3.0 mL, 0.36 mmol) which is synthesized according to the procedure for Step 3 of Example 16. The Argon gas is bubbled through the solution for 5 min. Then PdCl2dppf (11 mg, 0.015 mmol) is added. The mixture is heated at 100° C. for 3.5 hrs before EtOAc (15 mL) and water (15 mL) are added. The aqueous layer is separated and extracted with EtOAc (2×10 mL). The organic layers are combined and concentrated to give the crude product. Purification by flash column chromatography affords 8.0 mg of the titled product.

Workup

  1. customis synthesized
  2. customThe Argon gas is bubbled through the solution for 5 min
  3. additionare added
  4. customThe aqueous layer is separated
  5. extractionextracted with EtOAc (2×10 mL)
  6. concentrationconcentrated
  7. customto give the crude product
  8. customPurification by flash column chromatography

Sources & evidence

ORD record
ord-ec619efa9afa458ebc4b8e7e44bc6e5f
Source dataset
uspto-grants-2015_11
Patent number
US09181272B2

Reaction notes

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