1,4-Dioxane → 5-(2-methoxyphenyl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide

HRID 1473422노트

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HRID 1473422 반응식
Br[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6]([S:12]([N:15](CC1C=CC(OC)=CC=1OC)[C:16]1[S:20][N:19]=[CH:18][N:17]=1)(=[O:14])=[O:13])=[CH:7]2.[CH3:32][O:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=1B(O)O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>O>[CH3:32][O:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=1[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6]([S:12]([NH:15][C:16]1[S:20][N:19]=[CH:18][N:17]=1)(=[O:14])=[O:13])=[CH:7]2

참가 물질

6

반응물 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 27339582-Methoxyphenylboronic acidHCID 866873455-bromo-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide2회

생성물 1

HCID 715865115-(2-methoxyphenyl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide수율 74%

시약·촉매·용매 1

HCID 962Water용매2회

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온도
100 °C

실험 절차

A vial was charged with 5-bromo-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide (INTERMEDIATE D) (73.69 mg, 0.142 mmol), 2-methoxyphenylboronic acid (43.0 mg, 0.283 mmol), Pd(AmPhos)2Cl2 (5.01 mg, 7.08 μmol), potassium phosphate (90 mg, 0.425 mmol), 1,4-dioxane (708 μl), and water (236 μl). The vial was sealed and heated in a microwave reactor for 30 min at 100° C. The mixture was diluted with water and extracted with EtOAc (3×). The combined organic extracts were concentrated. The residue was dissolved in DCM (1 mL) and TFA (0.5 mL). After 2 h, the mixture was diluted with MeOH and filtered through diatomaceous earth with the aid of DCM. The filtrate was concentrated. The residue was purified twice by chromatography on silica gel (12-g columns, first with 0 to 5% MeOH/DCM, then with 2.5% MeOH/DCM), and the resulting material was dissolved in DCM and loaded onto a 1-g PE-AX ion exchange column (Biotage AB, Uppsala, Sweden). The column was flushed with 1:1 MeOH/DCM, then eluted with 10% HCl/MeOH (made by dissolving 1 mL on conc. HCl in 9 mL of MeOH). The acidic fraction was concentrated to give 5-(2-methoxyphenyl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide (41.62 mg, 0.105 mmol, 74.0% yield) as an off-white solid: 1H NMR (400 MHz, DMSO-d6) δ ppm=8.59-8.44 (m, 2H), 8.20 (d, J=8.2 Hz, 1H), 7.77-7.66 (m, 2H), 7.58 (d, J=8.9 Hz, 1H), 7.54-7.45 (m, 2H), 7.26-7.16 (m, 2H), 7.13-7.05 (m, 1H), 3.63 (s, 3H); m/z (ESI) 398.2 (M+H)+.

후처리

  1. customThe vial was sealed
  2. extractionextracted with EtOAc (3×)
  3. concentrationThe combined organic extracts were concentrated
  4. dissolutionThe residue was dissolved in DCM (1 mL)
  5. additionthe mixture was diluted with MeOH
  6. filtrationfiltered through diatomaceous earth with the aid of DCM
  7. concentrationThe filtrate was concentrated
  8. customThe residue was purified twice by chromatography on silica gel (12-g columns
  9. dissolutionfirst with 0 to 5% MeOH/DCM, then with 2.5% MeOH/DCM), and the resulting material was dissolved in DCM
  10. customThe column was flushed with 1:1 MeOH/DCM
  11. washeluted with 10% HCl/MeOH (made by dissolving 1 mL on conc. HCl in 9 mL of MeOH)
  12. concentrationThe acidic fraction was concentrated

출처 및 근거

ORD 기록
ord-a310dfd6900745c38ba1f566b5438507
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09012443B2

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