Hydrochloride methanol → 1-(3-Bromophenyl)-4-fluoro-1-(5-methoxy-4,6-dimethylpyridin-2-yl)-1H-isoindol-3-amine

HRID 1662197노트

반응식

HRID 1662197 반응식
C([Li])(C)(C)C.Br[C:7]1[N:12]=[C:11]([CH3:13])[C:10]([O:14][CH3:15])=[C:9]([CH3:16])[CH:8]=1.[Br:17][C:18]1[CH:19]=[C:20](/[C:24](/[C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[C:33]=2[C:39]#[N:40])=[N:25]\S(C(C)(C)C)=O)[CH:21]=[CH:22][CH:23]=1.Cl.CO>C1COCC1>[Br:17][C:18]1[CH:19]=[C:20]([C:24]2([C:7]3[CH:8]=[C:9]([CH3:16])[C:10]([O:14][CH3:15])=[C:11]([CH3:13])[N:12]=3)[C:32]3[C:33](=[C:34]([F:38])[CH:35]=[CH:36][CH:37]=3)[C:39]([NH2:40])=[N:25]2)[CH:21]=[CH:22][CH:23]=1

참가 물질

6

반응물 4

HCID 21893726Hydrochloride methanolHCID 58579486HCID 58579486, 화합물HCID 593275316-Bromo-3-methoxy-2,4-dimethylpyridineHCID 178418306HCID 178418306, 화합물

생성물 1

HCID 585795341-(3-Bromophenyl)-4-fluoro-1-(5-methoxy-4,6-dimethylpyridin-2-yl)-1H-isoindol-3-amine수율 84%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매3회

실험 절차

tert-Butyllithium (1.040 mL, 1.77 mmol) was added dropwise to THF (5 mL) at −100° C. under an argon atmosphere. A solution of 6-bromo-3-methoxy-2,4-dimethylpyridine (191 mg, 0.88 mmol) in THF (3 ml) was added dropwise followed by the addition of (E)-N-((3-bromophenyl)(2-cyano-3-fluorophenyl)methylene)-2-methylpropane-2-sulfinamide (300 mg, 0.74 mmol) in THF (7 ml). The resulting reaction mixture was left on the thawing cooling bath for 30 min then the cooling bath was removed and the mixture was stirred at r.t. for 1 h. Hydrogen chloride-methanol solution (3.54 mL, 4.42 mmol) was added and the resulting mixture was stirred at r.t. for 1 h. The mixture was concentrated under reduced pressure and the residue was purified on a silica gel column eluted with 0-10% 0.1 M NH3 in MeOH in DCM to give the title compound (272 mg, 84%). MS (ES+) m/z 440, 442 [M+1]+.

후처리

  1. customThe resulting reaction mixture
  2. waitwas left on the thawing
  3. temperaturecooling bath for 30 min
  4. customthe cooling bath was removed
  5. stirringthe resulting mixture was stirred at r.t. for 1 h
  6. concentrationThe mixture was concentrated under reduced pressure
  7. customthe residue was purified on a silica gel column
  8. washeluted with 0-10% 0.1 M NH3 in MeOH in DCM

출처 및 근거

ORD 기록
ord-be94451a988240a79721990a1fc634a4
출처 데이터셋
uspto-grants-2011_10
특허 번호
US08030500B2

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