4-Methylmorpholine → 4-[4-(3-cyclohexylpropoxy)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

HRID 1475905노트

반응식

HRID 1475905 반응식
[CH:1]1([CH2:7][CH2:8][CH2:9][O:10][C:11]2[CH:16]=[CH:15][N:14]([CH2:17][CH2:18][C:19]([CH3:27])([S:23]([CH3:26])(=[O:25])=[O:24])[C:20](O)=[O:21])[C:13](=[O:28])[CH:12]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CN1CCOCC1.[O:36]1[CH2:41][CH2:40][CH2:39][CH2:38][CH:37]1[O:42][NH2:43]>O>[CH:1]1([CH2:7][CH2:8][CH2:9][O:10][C:11]2[CH:16]=[CH:15][N:14]([CH2:17][CH2:18][C:19]([CH3:27])([S:23]([CH3:26])(=[O:25])=[O:24])[C:20]([NH:43][O:42][CH:37]3[CH2:38][CH2:39][CH2:40][CH2:41][O:36]3)=[O:21])[C:13](=[O:28])[CH:12]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

참가 물질

5

반응물 3

HCID 79724-MethylmorpholineHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 672616014-(4-(3-Cyclohexylpropoxy)-2-oxopyridin-1(2h)-yl)-2-methyl-2-(methylsulfonyl)butanoic acid

생성물 1

HCID 866719714-[4-(3-cyclohexylpropoxy)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide수율 95.2%

시약·촉매·용매 1

HCID 962Water용매

실험 절차

4-[4-(3-Cyclohexylpropoxy)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanoic acid (190 mg, 0.451 mmol) and CDMT (95.6 mg, 0.539 mmol) were charged into a flask. The flask was flushed with nitrogen and 2-MeTHF (10 ml) was added, followed by NMM (64 uL, 0.581 mmol). The reaction mixture was stirred at RT for 1 hour. O-(tetrahydro-2H-pyran-2-yl)hydroxylamine (64 mg, 0.539 mmol) was added to the reaction mixture and stirred for 16 hours at RT. Water (25 ml) was added, the layers were separated and the aqueous layer was extracted with EtOAc (3×50 ml). The organic layers were combined and dried over sodium sulfate, filtered and concentrated in vacuo. Crude material was purified by chromatography on silica gel (70% heptane:30% ethyl acetate to 100% ethyl acetate) to afford a white solid (220 mg, 79%). MS (LC/MS) m/z 511.1 (M−1) 1H NMR (400 MHz, METHANOL-d4) δ ppm 0.93 (t, J=7.02 Hz, 3H) 1.12-1.42 (m, 9H) 1.49-1.99 (m, 10H) 2.25-2.43 (m, 1H) 2.45-2.64 (m, 1H) 3.12 (d, J=5.07 Hz, 3H) 3.51-3.68 (m, 2H) 3.82-4.03 (m, 4H) 4.08-4.26 (m, 2H) 5.03-5.14 (m, 1H) 5.94 (d, J=2.54 Hz, 1H) 6.07-6.21 (m, 1H) 7.45-7.60 (m, 1H).

후처리

  1. customThe flask was flushed with nitrogen and 2-MeTHF (10 ml)
  2. additionwas added
  3. stirringstirred for 16 hours at RT
  4. customthe layers were separated
  5. extractionthe aqueous layer was extracted with EtOAc (3×50 ml)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customCrude material was purified by chromatography on silica gel (70% heptane:30% ethyl acetate to 100% ethyl acetate)

출처 및 근거

ORD 기록
ord-709bc8a102954a199785bfdb6fa2cb33
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09018384B2

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