Dimethylformamide → 8-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)-[1,6]naphthyridine

HRID 751315ノート

反応式

HRID 751315 の反応式
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[CH:7]2.[N:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[C:18]1[C:19](B(O)O)=[C:20]2[CH2:25][CH2:24][CH2:23][N:21]2[N:22]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CN(C=O)C>O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[N:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[C:18]1[C:19]([C:2]2[CH:3]=[N:4][CH:5]=[C:6]3[C:11]=2[N:10]=[CH:9][CH:8]=[CH:7]3)=[C:20]2[CH2:25][CH2:24][CH2:23][N:21]2[N:22]=1

参加物

7

反応物 4

HCID 6228DimethylformamideHCID 62657Potassium Phosphate, TribasicHCID 8172708-Bromo-1,6-naphthyridineHCID 59710031(2-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-3-boronic acid

生成物 1

HCID 586119458-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)-[1,6]naphthyridine収率 65.1%

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒2 回

反応条件

温度
60 °C

実験手順

Add 8-bromo-[1,6]naphthyridine (Spec; 32 mg, 0.152 mmol), 2-(pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-3-boronic acid (Preparation 5; 35 mg, 0.153 mmol), and potasium phosphate (97 mg, 0.458 mmol) to DMF (1 mL) and water (0.5 mL). De-gas the solution with argon and add tetrakis(triphenylphosphine)palladium(0) (88 mg, 0.076 mol). Heat the mixture at 60° C. for 18 h under an argon atmosphere. Cool the mixture to room temperature and dilute with water. Filter the mixture, and separate the filtrate. Extract the aqueous layer with dichloromethane. Dry the combined organic layers over sodium sulfate, filter, and concentrate. Purify the crude residue by column chromatography (12 g Redisep column, gradient dichloromethane through CMA over 40 min, 20 mL/min) to provide the title compound (31 mg, 64%) as an off white solid. Mp 180-184° C. MS (APCI) m/e=314 (M+1). 1H NMR (CDCl3) δ 8.88 (dd, J=1.6, 4.2 Hz, 1H), 8.60 (d, J=4.7 Hz, 1H), 8.28 (d, J=8.5 Hz, 1H), 8.19 (d, J=8.9 Hz, 1H), 7.73-7.68 (m, 3H), 7.58 (dd, J=4.2, 8.5 Hz, 2H), 4.30 (t, J=7 Hz, 2H), 3.30 (t, J=7 Hz, 2H), 2.73 (p, J=7 Hz, 2H). HPLC: >99%, Rt=7.1 min.

後処理

  1. customDe-gas the solution with argon
  2. temperatureCool the mixture to room temperature
  3. filtrationFilter the mixture
  4. customseparate the filtrate
  5. extractionExtract the aqueous layer with dichloromethane
  6. dry with materialDry the combined organic layers over sodium sulfate
  7. filtrationfilter
  8. concentrationconcentrate
  9. customPurify the crude residue by column chromatography (12 g Redisep column, gradient dichloromethane through CMA over 40 min, 20 mL/min)

出典と根拠

ORDレコード
ord-c2784340ab4c483da4f3f6ac10012af5
出典データセット
uspto-grants-2008_07
特許番号
US07405299B2

反応ノート

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