1,4-Dioxane → tert-butyl 6-(N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-3-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate

HRID 1524395노트

반응식

HRID 1524395 반응식
Br[C:2]1[C:10]2[C:5](=[N:6][C:7]([S:11](=[O:30])(=[O:29])[N:12]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][C:20]=3[O:27][CH3:28])[C:13]3[S:17][N:16]=[CH:15][N:14]=3)=[CH:8][CH:9]=2)[N:4]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH:3]=1.[CH3:38][N:39]1[C:43]([C:44]2[CH:49]=[C:48]([C:50]([F:53])([F:52])[F:51])[CH:47]=[CH:46][C:45]=2B(O)O)=[CH:42][CH:41]=[N:40]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>O>[CH3:28][O:27][C:20]1[CH:21]=[C:22]([O:25][CH3:26])[CH:23]=[CH:24][C:19]=1[CH2:18][N:12]([C:13]1[S:17][N:16]=[CH:15][N:14]=1)[S:11]([C:7]1[N:6]=[C:5]2[N:4]([C:31]([O:33][C:34]([CH3:35])([CH3:37])[CH3:36])=[O:32])[CH:3]=[C:2]([C:45]3[CH:46]=[CH:47][C:48]([C:50]([F:53])([F:51])[F:52])=[CH:49][C:44]=3[C:43]3[N:39]([CH3:38])[N:40]=[CH:41][CH:42]=3)[C:10]2=[CH:9][CH:8]=1)(=[O:29])=[O:30]

참가 물질

6

반응물 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 71258947(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)boronic acidHCID 71259315tert-butyl 3-bromo-6-(N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate

생성물 1

HCID 71259620tert-butyl 6-(N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-3-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate수율 71.3%

시약·촉매·용매 1

HCID 962Water용매

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온도
90 °C

실험 절차

A vial was charged with tert-butyl 3-bromo-6-(N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (531.8 mg, 0.871 mmol), (2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)boronic acid (306 mg, 1.132 mmol), potassium phosphate (555 mg, 2.61 mmol), and Pd(AmPhos)2Cl2 (30.8 mg, 0.044 mmol). 1,4-Dioxane (2178 μl) and water (726 μl) were added in sequence. The vial was sealed and heated in a microwave reactor for 30 min at 90° C. The organic layer was removed via pipette, and the aq. layer was extracted with EtOAc (2×). The combined organic extracts were concentrated in vacuo. The crude product was purified by chromatography on silica gel (0 to 50% EtOAc/Heptane) to give tert-butyl 6-(N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-3-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (469 mg, 0.621 mmol, 71.2% yield) as a white solid. m/z (ESI) 756.2 (M+H)+.

후처리

  1. customThe vial was sealed
  2. customThe organic layer was removed via pipette
  3. extractionthe aq. layer was extracted with EtOAc (2×)
  4. concentrationThe combined organic extracts were concentrated in vacuo
  5. customThe crude product was purified by chromatography on silica gel (0 to 50% EtOAc/Heptane)

출처 및 근거

ORD 기록
ord-36526f0170a44df7a71f845b6bc21a1c
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09079902B2

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