Triethylamine → (S)-2-(4-(5-(4-isopropyl-2-oxooxazolidin-3-yl)pyrazolo[1,5-a]pyrimidin-3-yl)benzoyl)hydrazinecarbothioamide

HRID 539001Notes

Reaction equation

HRID 539001 reaction equation
CCN=C=NCCCN(C)C.[CH:12]([C@H:15]1[CH2:19][O:18][C:17](=[O:20])[N:16]1[C:21]1[CH:26]=[CH:25][N:24]2[N:27]=[CH:28][C:29]([C:30]3[CH:38]=[CH:37][C:33]([C:34](O)=[O:35])=[CH:32][CH:31]=3)=[C:23]2[N:22]=1)([CH3:14])[CH3:13].C1C=CC2N(O)N=NC=2C=1.O.[NH:50]([C:52](=[S:54])[NH2:53])[NH2:51].C(N(CC)CC)C>CN(C=O)C.CCOC(C)=O>[CH:12]([C@H:15]1[CH2:19][O:18][C:17](=[O:20])[N:16]1[C:21]1[CH:26]=[CH:25][N:24]2[N:27]=[CH:28][C:29]([C:30]3[CH:31]=[CH:32][C:33]([C:34]([NH:51][NH:50][C:52](=[S:54])[NH2:53])=[O:35])=[CH:37][CH:38]=3)=[C:23]2[N:22]=1)([CH3:13])[CH3:14]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 2723789ThiosemicarbazideHCID 27960291-Hydroxybenzotriazole hydrateHCID 67034480(S)-4-(5-(4-isopropyl-2-oxooxazolidin-3-yl)pyrazolo[1,5-a]pyrimidin-3-yl)benzoic acid

Product 1

HCID 86667822(S)-2-(4-(5-(4-isopropyl-2-oxooxazolidin-3-yl)pyrazolo[1,5-a]pyrimidin-3-yl)benzoyl)hydrazinecarbothioamideYield 33.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

EDCI (157 mg, 0.819 mmol) was added to a mixture of (S)-4-(5-(4-isopropyl-2-oxooxazolidin-3-yl)pyrazolo[1,5-a]pyrimidin-3-yl)benzoic acid (Example 9, Step 1; 50 mg, 0.136 mmol) and HOBT-H2O (62.7 mg, 0.409 mmol) in DMF (2 mL) at ambient temperature, and the reaction mixture was stirred for 20 minutes at ambient temperature. 1.0 mL of hydrazinecarbothioamide (12.4 mg, 0.136 mmol) in DMF and triethylamine (95 μL, 0.682 mmol) were added. The resulting mixture was stirred for 1 hour at ambient temperature. The reaction mixture was diluted with EtOAc, washed with aqueous NH4Cl, NaHCO3, and brine, dried over MgSO4, and concentrated under reduced pressure. The crude material was purified by silica gel flash column chromatography (0-5% MeOH in dichloromethane) to afford 20.2 mg (21%) of (S)-2-(4-(5-(4-isopropyl-2-oxooxazolidin-3-yl)pyrazolo[1,5-a]pyrimidin-3-yl)benzoyl)hydrazinecarbothioamide. LCMS (APCI−) m/z 438.4 [M−H]+.

Workup

  1. stirringThe resulting mixture was stirred for 1 hour at ambient temperature
  2. washwashed with aqueous NH4Cl, NaHCO3, and brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated under reduced pressure
  5. customThe crude material was purified by silica gel flash column chromatography (0-5% MeOH in dichloromethane)

Sources & evidence

ORD record
ord-918dba0c01564fd0b80afe279743fcd7
Source dataset
uspto-grants-2014_10
Patent number
US08865726B2

Reaction notes

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