Sodium Carbonate → 4-(7-chloro-1H-indazol-5-yl)-isoquinoline

HRID 402132노트

반응식

HRID 402132 반응식
[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](B(O)O)=[CH:3][N:2]=1.Br[C:15]1[CH:16]=[C:17]2[C:21](=[C:22]([Cl:24])[CH:23]=1)[NH:20][N:19]=[CH:18]2.C(=O)([O-])[O-].[Na+].[Na+]>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.C(COC)OC>[Cl:24][C:22]1[CH:23]=[C:15]([C:4]2[C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[CH:1]=[N:2][CH:3]=2)[CH:16]=[C:17]2[C:21]=1[NH:20][N:19]=[CH:18]2

참가 물질

6

반응물 3

HCID 10340Sodium CarbonateHCID 3761204Isoquinoline-4-boronic acidHCID 211021945-Bromo-7-chloro-1H-indazole

생성물 1

HCID 689979964-(7-chloro-1H-indazol-5-yl)-isoquinoline수율 72.1%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 80711,2-Dimethoxyethane용매

반응 조건

온도
85 °C

실험 절차

A mixture of isoquinolin-4-ylboronic acid (1.00 g, 5.78 mmol), 5-bromo-7-chloro-1H-indazole (892 mg, 3.85 mmol), 2.0 M sodium carbonate (3.85 mL, 7.71 mmol) and dimethoxyethane was degassed with argon. Tetrakis(triphenylphosphine)palladium(0) (233 mg, 0.193 mmol) was added, the mixture degassed again with argon, then heated to 85° C. for 24 hours. The reaction was cooled and partitioned between ethyl acetate and water, the organic layer washed with and dried with sodium sulfate. The solvent was removed under vacuum and the residue purified by column chromatography (9/1 to 6/4 hexanes/ethyl acetate gradient) to give 4-(7-chloro-1H-indazol-5-yl)-isoquinoline (777 mg, 72%): 1H NMR (300 MHz, CDCl3) δ 10.52 (s, 1H) 9.31 (s, 1H), 8.53 (s, 1H), 8.22 (s, 1H), 8.09 (dd, J=7.4, 1.62 Hz, 1H), 7.28 (dd, J=7.4, 1.2 Hz, 1H), 7.87 (d, J=9.0 Hz, 1H), 7.81 (d, J=1.2 Hz, 1H), 7.72-7.64 (m, 2H), 7.57 (d, J=1.3 Hz, 1H).

후처리

  1. customwas degassed with argon
  2. customthe mixture degassed again with argon
  3. temperatureThe reaction was cooled
  4. custompartitioned between ethyl acetate and water
  5. washthe organic layer washed with and
  6. dry with materialdried with sodium sulfate
  7. customThe solvent was removed under vacuum
  8. customthe residue purified by column chromatography (9/1 to 6/4 hexanes/ethyl acetate gradient)

출처 및 근거

ORD 기록
ord-2e5a62837c3e46369bf7b0d9a303a0dd
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08741901B2

반응 노트

불러오는 중…