5-Amino-2-methylbenzenesulfonamide → HCID 178426361, 화합물

HRID 474378

반응식

HRID 474378 반응식
[C:1]([O:5][C:6](=[O:25])[NH:7][C@H:8]1[CH2:13][CH2:12][C@@H:11]([CH2:14][N:15]2[C:19]3=[N:20][C:21](Cl)=[N:22][CH:23]=[C:18]3[CH:17]=[N:16]2)[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[NH2:26][C:27]1[CH:28]=[CH:29][C:30]([CH3:37])=[C:31]([S:33]([NH2:36])(=[O:35])=[O:34])[CH:32]=1.CC(C)([O-])C.[Na+].C(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C>O1CCOCC1.CCOC(C)=O.O>[C:1]([O:5][C:6](=[O:25])[NH:7][C@H:8]1[CH2:13][CH2:12][C@@H:11]([CH2:14][N:15]2[C:19]3=[N:20][C:21]([NH:26][C:27]4[CH:28]=[CH:29][C:30]([CH3:37])=[C:31]([S:33](=[O:35])(=[O:34])[NH2:36])[CH:32]=4)=[N:22][CH:23]=[C:18]3[CH:17]=[N:16]2)[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2]

참가 물질

8

반응물 4

HCID 2355115-Amino-2-methylbenzenesulfonamideHCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneHCID 23676156Sodium t-butoxideHCID 178453936HCID 178453936, 화합물

생성물 1

HCID 178426361HCID 178426361, 화합물수율 25%

시약·촉매·용매 3

HCID 962Water용매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매2회

실험 절차

A solution of tert-butyl-cis-4-((6-chloro-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)cyclohexylcarbamate (1.66 g, 4.53 mmol, prepared using A from Preparation #2 and tert-butyl-cis-(4-hydroxymethyl)cyclohexylcarbamate [AMRI]), 5-amino-2-methylbenzenesulfonamide (1.10 g, 5.89 mmol, Waterstone), and sodium tert-butoxide (1.306 g, 13.59 mmol) in 1,4-dioxane (15 mL) was stirred at ambient temperature for about 30 min. In a separate 10 mL nitrogen purged vial charged with Pd2(dibenzylideneacetone)3 (0.415 g, 0.453 mmol) and 2-di-tert-butylphosphino-2′,4′,6′-triisopropylbiphenyl (0.789 g, 1.86 mmol) was added 1,4-dioxane (2 mL) followed by heating to about 80° C. for about 2 min. The mixture was subsequently cooled to ambient temperature. The catalyst solution was added to the reaction mixture at ambient temperature and the reaction mixture was heated to about 80° C. for about 16 h. The reaction mixture was cooled to ambient temperature then water (100 mL) and EtOAc (50 mL) were added and the organic layer was separated. The aqueous layer was further extracted with EtOAc (2×50 mL) and the combined organic extracts were dried over anhydrous MgSO4, filtered through a silica gel pad, and concentrated under reduced pressure. The crude residue was purified by silica gel chromatography eluting with 50% EtOAc in heptane to provide tert-butyl-cis-4-((6-(4-methyl-3-sulfamoylphenylamino)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)cyclohexylcarbamate (0.58 g, 25%) as a light yellow solid. LC/MS (Table 2, Method a) Rt=1.38 min; MS m/z: 516 (M+H)+.

후처리

  1. temperatureby heating to about 80° C. for about 2 min
  2. temperatureThe mixture was subsequently cooled to ambient temperature
  3. additionThe catalyst solution was added to the reaction mixture at ambient temperature
  4. temperaturethe reaction mixture was heated to about 80° C. for about 16 h
  5. temperatureThe reaction mixture was cooled to ambient temperature
  6. customthe organic layer was separated
  7. extractionThe aqueous layer was further extracted with EtOAc (2×50 mL)
  8. dry with materialthe combined organic extracts were dried over anhydrous MgSO4
  9. filtrationfiltered through a silica gel pad
  10. concentrationconcentrated under reduced pressure
  11. customThe crude residue was purified by silica gel chromatography
  12. washeluting with 50% EtOAc in heptane

출처 및 근거

ORD 기록
ord-7ff0f2b535c34ac796a5e9bc998ce074
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08637529B2

연결된 노트

불러오는 중…