Carbon Tetrachloride → (S)-3-(3-(4-(5-(2-hydroxyethylamino)-1,3,4-oxadiazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-isopropyloxazolidin-2-one

HRID 539007노트

반응식

HRID 539007 반응식
[OH:1][CH2:2][CH2:3][NH:4][C:5]([NH:7][NH:8][C:9](=O)[C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH:17]=[N:18][N:19]3[CH:24]=[CH:23][C:22]([N:25]4[C@@H:29]([CH:30]([CH3:32])[CH3:31])[CH2:28][O:27][C:26]4=[O:33])=[N:21][C:20]=23)=[CH:12][CH:11]=1)=[O:6].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(N(CC)CC)C.C(Cl)(Cl)(Cl)Cl>ClCCl.CC#N.CCOC(C)=O>[OH:1][CH2:2][CH2:3][NH:4][C:5]1[O:6][C:9]([C:10]2[CH:11]=[CH:12][C:13]([C:16]3[CH:17]=[N:18][N:19]4[CH:24]=[CH:23][C:22]([N:25]5[C@@H:29]([CH:30]([CH3:32])[CH3:31])[CH2:28][O:27][C:26]5=[O:33])=[N:21][C:20]=34)=[CH:14][CH:15]=2)=[N:8][N:7]=1

참가 물질

8

반응물 4

HCID 5943Carbon TetrachlorideHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 67033962(S)-N-(2-hydroxyethyl)-2-(4-(5-(4-isopropyl-2-oxooxazolidin-3-yl)pyrazolo[1,5-a]pyrimidin-3-yl)benzoyl)hydrazinecarboxamide

생성물 1

HCID 68088822(S)-3-(3-(4-(5-(2-hydroxyethylamino)-1,3,4-oxadiazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-isopropyloxazolidin-2-one수율 35.9%

시약·촉매·용매 3

HCID 6342Acetonitrile용매HCID 6344Dichloromethane용매HCID 8857Ethyl Acetate용매

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온도
50 °C

실험 절차

To a suspension of (S)—N-(2-hydroxyethyl)-2-(4-(5-(4-isopropyl-2-oxooxazolidin-3-yl)pyrazolo[1,5-a]pyrimidin-3-yl)benzoyl)hydrazinecarboxamide (14.4 mg, 0.031 mmol) in dichloromethane (1 mL) and MeCN (1 mL) was added PS-triphenylphosphine resin (0.054 g, 2.28 mmol/g, 0.123 mmol), triethylamine (44 μL, 0.308 mmol), and CCl4 (12 μL, 0.123 mmol), and the reaction mixture was heated to 50° C. for 4 hours. After the mixture was cooled at ambient temperature, the reaction mixture was treated with EtOAc, washed with water, dried over MgSO4, and concentrated under reduced pressure. The crude was then purified by preparative plate silica gel chromatography (10% MeOH in dichloromethane) to afford 5 mg (35%) of (S)-3-(3-(4-(5-(2-hydroxyethylamino)-1,3,4-oxadiazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-isopropyloxazolidin-2-one. 1H NMR (400 MHz, CDCl3) δ 8.60 (d, 1H), 8.43 (s, 1H), 8.08 (m, 3H), 7.92 (d, 2H), 4.96 (m, 1H), 4.44 (m, 2H), 3.94 (t, 2H), 3.65 (m, 2H), 2.88 (m, 1H), 1.09 (d, 3H), 0.95 (d, 3H); LCMS (APCI+) m/z 450.6 [M+H]+.

후처리

  1. temperatureAfter the mixture was cooled at ambient temperature
  2. washwashed with water
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated under reduced pressure
  5. customThe crude was then purified by preparative plate silica gel chromatography (10% MeOH in dichloromethane)

출처 및 근거

ORD 기록
ord-e50f7a0467164d5bb4fb69c7ad7c2e79
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08865726B2

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