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

HRID 712649노트

반응식

HRID 712649 반응식
[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]

참가 물질

9

반응물 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

생성물 1

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

시약·촉매·용매 5

HCID 178418476HCID 178418476, 화합물촉매HCID 702Ethanol용매HCID 962Water용매HCID 6344Dichloromethane용매HCID 80711,2-Dimethoxyethane용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-495ff894c9d942abb0fd2a4c38d113e0
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09181272B2

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