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

HRID 712649ノート

反応式

HRID 712649 の反応式
[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]

参加物

9

反応物 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

生成物 1

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

試薬・触媒・溶媒 5

HCID 178418476HCID 178418476、化合物触媒HCID 702Ethanol溶媒HCID 962Water溶媒HCID 6344Dichloromethane溶媒HCID 80711,2-Dimethoxyethane溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-495ff894c9d942abb0fd2a4c38d113e0
出典データセット
uspto-grants-2015_11
特許番号
US09181272B2

反応ノート

読み込み中…