Triethylamine → (S)-2-amino-N-(5-(4-(methylsulfonyl)phenyl)pent-4-ynyl)butanamide

HRID 473512노트

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HRID 473512 반응식
[CH2:1]([NH:6][C:7](=[O:18])[C@@H:8]([NH:11]C(=O)C(F)(F)F)[CH2:9][CH3:10])[CH2:2][CH2:3][C:4]#[CH:5].[CH3:19][S:20]([C:23]1[CH:28]=[CH:27][C:26](Br)=[CH:25][CH:24]=1)(=[O:22])=[O:21].C(N(CC)CC)C.[OH-].[Na+]>CN(C=O)C.C1COCC1.CO.O.[I].[Cu].Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:11][C@@H:8]([CH2:9][CH3:10])[C:7]([NH:6][CH2:1][CH2:2][CH2:3][C:4]#[C:5][C:26]1[CH:27]=[CH:28][C:23]([S:20]([CH3:19])(=[O:22])=[O:21])=[CH:24][CH:25]=1)=[O:18]

참가 물질

11

반응물 4

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 770141-Bromo-4-(methylsulphonyl)benzeneHCID 86653105(S)-N-(pent-4-ynyl)-2-(2,2,2-trifluoroacetamido)butanamide

생성물 1

HCID 52919469(S)-2-amino-N-(5-(4-(methylsulfonyl)phenyl)pent-4-ynyl)butanamide

시약·촉매·용매 6

HCID 178418476HCID 178418476, 화합물촉매HCID 178505378HCID 178505378, 화합물촉매HCID 887Methanol용매HCID 962Water용매HCID 6228Dimethylformamide용매HCID 8028Tetrahydrofuran용매

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온도
70 °C

실험 절차

(S)—N-(pent-4-ynyl)-2-(2,2,2-trifluoroacetamido)butanamide (0.246 g, 0.93 mmol), 4-bromophenyl methyl sulfone (0.200 g, 0.85 mmol), triethylamine (5 ml), copper iodine (0.032 g, 0.17 mmol) and Pd(PPh3)2Cl2 (0.175 g, 0.25 mmol) were combined in anhydrous DMF (5 ml) and heated to 70° C. in a sealed tube overnight. The resulting mixture was then concentrated in vacuo and ethyl acetate (46 ml) was added to the remaining residue. The resulting mixture was washed with 1N HCl (2×23 ml), water (23 ml), brine (23 ml), dried (MgSO4) and concentrated in vacuo. The resulting residue was chromatographed eluting with ethyl acetate/heptanes (30:70) to yield a residue. The residue was dissolved in THF (0.5 ml)/MeOH (0.13 ml) and cooled to 0° C. 3N NaOH (0.10 ml, 0.30 mmol) was added, the resulting mixture was warmed to room temperature and stirred overnight. The resulting mixture was then diluted with water (0.25 ml) and concentrated in vacuo. The aqueous layer was extracted with methylene chloride (3×5 ml), dried (MgSO4) and concentrated in vacuo. The resulting residue was chromatographed eluting with methylene chloride/methanol (95:5) followed by elution with methylene chloride/methanol/ammonium hydroxide (95:5:0.4) to yield (S)-2-amino-N-(5-(4-(methylsulfonyl)phenyl)pent-4-ynyl)butanamide. ES-MS m/z 323 (MH+).

후처리

  1. concentrationThe resulting mixture was then concentrated in vacuo and ethyl acetate (46 ml)
  2. additionwas added to the remaining residue
  3. washThe resulting mixture was washed with 1N HCl (2×23 ml), water (23 ml), brine (23 ml)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was chromatographed
  7. washeluting with ethyl acetate/heptanes (30:70)
  8. customto yield a residue
  9. temperaturecooled to 0° C
  10. temperaturethe resulting mixture was warmed to room temperature
  11. concentrationconcentrated in vacuo
  12. extractionThe aqueous layer was extracted with methylene chloride (3×5 ml)
  13. dry with materialdried (MgSO4)
  14. concentrationconcentrated in vacuo
  15. customThe resulting residue was chromatographed
  16. washeluting with methylene chloride/methanol (95:5)
  17. washfollowed by elution with methylene chloride/methanol/ammonium hydroxide (95:5:0.4)

출처 및 근거

ORD 기록
ord-2d6771c680074223a10f2d7c907d875e
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08633322B2

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