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 539007ノート

反応式

HRID 539007 の反応式
[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

参加物

8

反応物 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

生成物 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-one収率 35.9%

試薬・触媒・溶媒 3

HCID 6342Acetonitrile溶媒HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
50 °C

実験手順

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]+.

後処理

  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)

出典と根拠

ORDレコード
ord-e50f7a0467164d5bb4fb69c7ad7c2e79
出典データセット
uspto-grants-2014_10
特許番号
US08865726B2

反応ノート

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