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

HRID 539002Notes

Reaction equation

HRID 539002 reaction equation
[CH:1]([C@H:4]1[CH2:8][O:7][C:6](=[O:9])[N:5]1[C:10]1[CH:15]=[CH:14][N:13]2[N:16]=[CH:17][C:18]([C:19]3[CH:31]=[CH:30][C:22]([C:23]([NH:25][NH:26][C:27](=[S:29])[NH2:28])=O)=[CH:21][CH:20]=3)=[C:12]2[N:11]=1)([CH3:3])[CH3:2].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(N(CC)CC)C.C(Cl)(Cl)(Cl)Cl>ClCCl.CCOC(C)=O>[NH2:28][C:27]1[S:29][C:23]([C:22]2[CH:30]=[CH:31][C:19]([C:18]3[CH:17]=[N:16][N:13]4[CH:14]=[CH:15][C:10]([N:5]5[C@@H:4]([CH:1]([CH3:3])[CH3:2])[CH2:8][O:7][C:6]5=[O:9])=[N:11][C:12]=34)=[CH:20][CH:21]=2)=[N:25][N:26]=1

Participants

7

Reactant 4

HCID 5943Carbon TetrachlorideHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 86667822(S)-2-(4-(5-(4-isopropyl-2-oxooxazolidin-3-yl)pyrazolo[1,5-a]pyrimidin-3-yl)benzoyl)hydrazinecarbothioamide

Product 1

HCID 67034573(S)-3-(3-(4-(5-amino-1,3,4-thiadiazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-isopropyloxazolidin-2-oneYield 7.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of (S)-2-(4-(5-(4-isopropyl-2-oxooxazolidin-3-yl)pyrazolo[1,5-a]pyrimidin-3-yl)benzoyl)hydrazinecarbothioamide (20.2 mg, 0.029 mmol) in dichloromethane (3 ml) was added PPh3 (22.7 mg, 0.087 mmol), triethylamine (32 μL, 0.231 mmol), and CCl4 (13.3 mg, 0.087 mmol). The reaction mixture was heated to 50° C. for 3 hours. After cooling to ambient temperature the reaction mixture was dissolved in EtOAc, washed with water then brine, dried over MgSO4, and concentrated under reduced pressure. The crude was purified by silica gel flash column chromatography (0-5% 7N NH3-MeOH in dichloromethane). The product was then subjected to preparative plate chromatography (10% MeOH in dichloromethane) to afford 0.9 mg (7%) of (S)-3-(3-(4-(5-amino-1,3,4-thiadiazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-isopropyloxazolidin-2-one. 1H NMR (400 MHz, CDCl3) δ 8.60 (d, 1H), 8.42 (s, 1H), 8.08 (m, 3H), 7.76 (d, 2H), 4.95 (m, 1H), 4.46 (m, 2H), 2.85 (m, 1H), 1.10 (d, 3H), 0.95 (d, 3H); LCMS (APCI+) m/z 422.5 [M+H]+.

Workup

  1. temperatureAfter cooling to ambient temperature the reaction mixture
  2. washwashed with water
  3. dry with materialbrine, dried over MgSO4
  4. concentrationconcentrated under reduced pressure
  5. customThe crude was purified by silica gel flash column chromatography (0-5% 7N NH3-MeOH in dichloromethane)

Sources & evidence

ORD record
ord-390cb25509ef4a378e6ae07799dc1be0
Source dataset
uspto-grants-2014_10
Patent number
US08865726B2

Reaction notes

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