Water → Methanesulfonic acid 7,9-difluoro-5-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-5H-6-thia-chrysen-2-yl ester

HRID 1513937노트

반응식

HRID 1513937 반응식
[F:1][C:2]1[C:3]([S:41]C)=[C:4]([C:9]2[C:10]([CH:24](O)[C:25]3[CH:30]=[CH:29][C:28]([O:31][CH2:32][CH2:33][N:34]4[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]4)=[CH:27][CH:26]=3)=[C:11]3[C:16](=[CH:17][CH:18]=2)[CH:15]=[C:14]([O:19][S:20]([CH3:23])(=[O:22])=[O:21])[CH:13]=[CH:12]3)[CH:5]=[C:6]([F:8])[CH:7]=1.C(N(CC)CC)C.CS(Cl)(=O)=O.O>C(Cl)Cl>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[C:4]2[C:3]=1[S:41][CH:24]([C:25]1[CH:26]=[CH:27][C:28]([O:31][CH2:32][CH2:33][N:34]3[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]3)=[CH:29][CH:30]=1)[C:10]1[C:9]2=[CH:18][CH:17]=[C:16]2[C:11]=1[CH:12]=[CH:13][C:14]([O:19][S:20]([CH3:23])(=[O:21])=[O:22])=[CH:15]2

참가 물질

6

반응물 4

HCID 962WaterHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 86626530Methanesulfonic acid 6-(3,5-difluoro-2-methylsulfanyl-phenyl)-5-{hydroxy-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methyl}-naphthalen-2-yl ester

생성물 1

HCID 11273238Methanesulfonic acid 7,9-difluoro-5-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-5H-6-thia-chrysen-2-yl ester수율 74.5%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

Dissolve methanesulfonic acid 6-(3,5-difluoro-2-methylsulfanyl-phenyl)-5-{hydroxy-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methyl}-naphthalen-2-yl ester (7.4 g, 12 mmol) in dry methylene chloride (200 mL) and purge with nitrogen. Add triethylamine (8.3 mL, 60 mmol) followed by methanesulfonyl chloride (4.6 mL, 60 mmol). After 30 minutes, pour reaction into water and extract with methylene chloride. Wash organic layer with water, dry over sodium sulfate, filter and concentrate. Purify over silica gel, eluting with 0 to 3% methanol in methylene chloride, to yield 5.2 g (74%) of the title compound. LCMS Rt (0.01% heptafluorobutyric acid:1.0% isopropylalcohol:water is mobile phase A and 0.01% heptafluorobutyric acid:1.0% isopropylalcohol:acetonitrile is mobile phase B; gradient method 25 to 95% B, Purity@254 nm)=3.34 min (100%); mass spectrum (ion spray): m/z=582.2 (M+H).

후처리

  1. custompurge with nitrogen
  2. additionpour
  3. extractionextract with methylene chloride
  4. dry with materialWash organic layer with water, dry over sodium sulfate
  5. filtrationfilter
  6. concentrationconcentrate
  7. customPurify over silica gel
  8. washeluting with 0 to 3% methanol in methylene chloride

출처 및 근거

ORD 기록
ord-12702aa45da542809866c81e3bc5c98e
출처 데이터셋
uspto-grants-2012_07
특허 번호
US08217032B2

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