Sodium Carbonate → 6-(4-carbamoyl-pyridin-3-yl)-3,4-dihydro-2H-[1,8]naphthyridine-1-carboxylic acid tert-butyl ester

HRID 712649Notes

Reaction equation

HRID 712649 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:17]2[C:12](=[CH:13][C:14](B3OC(C)(C)C(C)(C)O3)=[CH:15][N:16]=2)[CH2:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[C:28]1[CH:36]=[N:35][CH:34]=[CH:33][C:29]=1[C:30]([NH2:32])=[O:31].C([O-])([O-])=O.[Na+].[Na+]>COCCOC.CCO.C(Cl)Cl.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[C:17]2[C:12](=[CH:13][C:14]([C:33]3[CH:34]=[N:35][CH:36]=[CH:28][C:29]=3[C:30](=[O:31])[NH2:32])=[CH:15][N:16]=2)[CH2:11][CH2:10][CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

9

Reactant 3

HCID 10340Sodium CarbonateHCID 109765133-BromoisonicotinamideHCID 1232163436-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,4-dihydro-2H-[1,8]naphthyridine-1-carboxylic acid tert-butyl ester

Product 1

HCID 1176677496-(4-carbamoyl-pyridin-3-yl)-3,4-dihydro-2H-[1,8]naphthyridine-1-carboxylic acid tert-butyl esterYield 23.5%

Reagents, catalysts & solvents 5

HCID 178418476HCID 178418476, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

6-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,4-dihydro-2H-[1,8]naphthyridine-1-carboxylic acid tert-butyl ester (100 mg, 0.36 mmol), 3-bromo-isonicotinamide (80 mg, 0.40 mmol), saturated Na2CO3 aqueous solution (1.0 mL) and Pd(PPh3)2Cl2 (24 mg, 0.034 mmol) are mixed in DME (5.0 mL) and EtOH (5.0 mL). The reaction mixture is microwaved at 140° C. for 45 mins. Then mixture is diluted with DCM and water. The organic layer is separated and concentrated to give the crude product. Purification by flash column chromatography affords 30 mg 6-(4-carbamoyl-pyridin-3-yl)-3,4-dihydro-2H-[1,8]naphthyridine-1-carboxylic acid tert-butyl ester. It is then used to prepare 3-(5,6,7,8-tetrahydro-[1,8]naphthyridin-3-yl)-isonicotinamide according to the procedure for Step 2 of Example 27 using 20% trifluoroacetic acid in DCM as the reagent.

Workup

  1. customThe reaction mixture is microwaved at 140° C. for 45 mins
  2. customThe organic layer is separated
  3. concentrationconcentrated
  4. customto give the crude product
  5. customPurification by flash column chromatography

Sources & evidence

ORD record
ord-495ff894c9d942abb0fd2a4c38d113e0
Source dataset
uspto-grants-2015_11
Patent number
US09181272B2

Reaction notes

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