Dimethylformamide → N-{2-Bromo-6-methyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridin-4-yl}methanesulfonamide

HRID 573668노트

반응식

HRID 573668 반응식
[Br:1][C:2]1[S:12][C:5]2[N:6]=[C:7]([CH3:11])[CH:8]=[C:9]([NH2:10])[C:4]=2[C:3]=1[C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH3:20])[CH:14]=1.CC(C)([O-])C.[Na+].[CH3:27][S:28](Cl)(=[O:30])=[O:29].CN(C=O)C>C1COCC1.C(OCC)(=O)C.O>[Br:1][C:2]1[S:12][C:5]2=[N:6][C:7]([CH3:11])=[CH:8][C:9]([NH:10][S:28]([CH3:27])(=[O:30])=[O:29])=[C:4]2[C:3]=1[C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH3:20])[CH:14]=1

참가 물질

8

반응물 4

HCID 6228DimethylformamideHCID 31297Methanesulfonyl chloride2회HCID 23676156Sodium t-butoxide2회HCID 683240582-Bromo-6-methyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridin-4-amine

생성물 1

HCID 68323754N-{2-Bromo-6-methyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridin-4-yl}methanesulfonamide수율 32.2%

시약·촉매·용매 3

HCID 962Water용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

실험 절차

To a stirred solution of 2-bromo-6-methyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridin-4-amine (Description 17) (277 mg, 0.793 mmol) in THF (2.5 mL) at RT, was added sodium tert-butoxide (220 mg, 2.289 mmol). The reaction mixture was stirred at RT for 15 min, followed by the addition of methane sulfonyl chloride (0.14 mL, 1.797 mmol). The reaction mixture was stirred at 1 h at RT, followed by the addition of DMF (2.5 mL), another portion of sodium tert-butoxide (203 mg, 2.112 mmol) and methane sulfonyl chloride (0.14 mL, 1.797 mmol). The reaction mixture was stirred for another 1 h at RT before the addition of water (20 mL) and ethyl acetate (20 mL). The aqueous layer was separated and extracted with ethyl acetate (3×25 mL). The combined organic extracts were washed with water (15 mL), dried (phase separating column) and concentrated to give a residue. Purification on silica (twice), eluting with a gradient of 0-75% ethyl acetate in cyclohexane afforded the title compound (109 mg) which was of sufficient purity for subsequent steps. In addition, some impure fractions were isolated and these were combined and further purified by MDAP (acidic conditions), to give an analytically pure sample of the title compound (9 mg). LCMS (A) m/z: 427/429 [M+1]+, Rt 1.33 min (acidic).

후처리

  1. stirringThe reaction mixture was stirred at 1 h at RT
  2. customThe aqueous layer was separated
  3. extractionextracted with ethyl acetate (3×25 mL)
  4. washThe combined organic extracts were washed with water (15 mL)
  5. customdried
  6. custom(phase separating column)
  7. concentrationconcentrated
  8. customto give a residue
  9. customPurification on silica (twice),
  10. washeluting with a gradient of 0-75% ethyl acetate in cyclohexane

출처 및 근거

ORD 기록
ord-1f8c547bf6044e5e89c3eb9241e4529a
출처 데이터셋
uspto-grants-2015_05
특허 번호
US09029545B2

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