Hydrochloric Acid → N-((1R)-1-{4-[(hydroxyamino)carbonyl]phenyl}ethyl)-1-benzofuran-2-carboxamide

HRID 1049080노트

반응식

HRID 1049080 반응식
[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[CH:3]=[C:2]1[C:10]([NH:12][C@@H:13]([C:15]1[CH:27]=[CH:26][C:18]([C:19](OC(C)(C)C)=[O:20])=[CH:17][CH:16]=1)[CH3:14])=[O:11].FC(F)(F)C(O)=O.CN(C([O:42][N:43]1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C.[Si](ON)(C(C)(C)C)(C)C.Cl>CS(C)=O.C(Cl)Cl>[OH:42][NH:43][C:19]([C:18]1[CH:26]=[CH:27][C:15]([C@H:13]([NH:12][C:10]([C:2]2[O:1][C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=3[CH:3]=2)=[O:11])[CH3:14])=[CH:16][CH:17]=1)=[O:20]

참가 물질

9

반응물 6

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 4691350O-(tert-Butyldimethylsilyl)hydroxylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67395671tert-butyl 4-{(1R)-1-[(1-benzofuran-2-ylcarbonyl)amino]ethyl}benzoate

생성물 1

HCID 86657276N-((1R)-1-{4-[(hydroxyamino)carbonyl]phenyl}ethyl)-1-benzofuran-2-carboxamide수율 24%

시약·촉매·용매 2

HCID 679Dimethyl Sulfoxide용매HCID 6344Dichloromethane용매2회

실험 절차

To a 2-dram vial containing tert-butyl 4-{(1R)-1-[(1-benzofuran-2-ylcarbonyl)amino]ethyl}benzoate was added DCM (2.5 mL), and trifluoroacetic acid (0.28 mL, 3.60 mmol). The mixture was stirred at rt for 6 h then evaporated to give an oil residue. To the residue was added HATU (0.10 g, 0.27 mmol), triethylamine (0.25 mL, 1.80 mmol), and DCM (2.5 mL). After stirring at rt for 30 min, O-(tert-butyldimethylsilyl)hydroxylamine (0.053 g, 0.360 mmol) was added. The mixture was stirred at rt for 2 h, then the solvent was completely removed to give a sticky brown oil. To this oil residue was added hydrochloric acid (4.0 mL, 1% v/v in IPA). After stirring at rt for 30 min, the solvent was evaporated to dryness to give a solid. To the solid was then added DMSO (1.1 mL). The solution was filtered and purified by Gilson prep-HPLC [25-50% MeCN—H2O] to give N-((1R)-1-{4-[(hydroxyamino)carbonyl]phenyl}ethyl)-1-benzofuran-2-carboxamide (0.0148 g, 24%) as a white solid. LC-MS: (FA) ES+ 325; 1H NMR (Methanol-d4, 400 MHz) δ 7.71 (m, 3H), 7.60 (d, J=8.5 Hz, 1H), 7.50 (m, 3H), 7.45 (t, J=7.0 Hz, 1H), 7.31 (t, J=7.8 Hz, 1H), 5.30 (q, J=7.2 Hz, 1H), 1.61 (d, J=7.0 Hz, 3H).

후처리

  1. customthen evaporated
  2. customto give an oil residue
  3. stirringAfter stirring at rt for 30 min
  4. stirringThe mixture was stirred at rt for 2 h
  5. customthe solvent was completely removed
  6. customto give a sticky brown oil
  7. stirringAfter stirring at rt for 30 min
  8. customthe solvent was evaporated to dryness
  9. customto give a solid
  10. filtrationThe solution was filtered
  11. custompurified by Gilson prep-HPLC [25-50% MeCN—H2O]

출처 및 근거

ORD 기록
ord-d02457ca831041adae5837fe8d23069a
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09382197B2

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