Cyanogen Bromide → (S)-3-(3-(4-(5-amino-1,3,4-oxadiazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-isopropyloxazolidin-2-one

HRID 539000Notes

Reaction equation

HRID 539000 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:28]=[CH:27][C:22]([C:23]([NH:25][NH2:26])=[O:24])=[CH:21][CH:20]=3)=[C:12]2[N:11]=1)([CH3:3])[CH3:2].[N:29]#[C:30]Br.C([O-])(O)=O.[Na+]>O1CCOCC1.O.CCOC(C)=O>[NH2:29][C:30]1[O:24][C:23]([C:22]2[CH:27]=[CH:28][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 3

HCID 10476Cyanogen BromideHCID 516892Sodium BicarbonateHCID 67033928(S)-4-(5-(4-isopropyl-2-oxooxazolidin-3-yl)pyrazolo[1,5-a]pyrimidin-3-yl)benzohydrazide

Product 1

HCID 67034339(S)-3-(3-(4-(5-amino-1,3,4-oxadiazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-isopropyloxazolidin-2-oneYield 49%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To a suspension of (S)-4-(5-(4-isopropyl-2-oxooxazolidin-3-yl)pyrazolo[1,5-a]pyrimidin-3-yl)benzohydrazide (50 mg, 0.131 mmol) in 3 mL of p-dioxane was added cyanogen bromide (30.6 mg, 0.289 mmol) followed by a solution of NaHCO3 (13.3 mg, 0.158 mmol) in 1.5 mL of water. The resulting mixture became a clear tan solution within 3 minutes, and was allowed to stir at ambient temperature for 17 hours. The reaction was diluted with EtOAc, and the organic layer was washed with water and brine. The combined organic layers were dried over MgSO4 and concentrated under reduced pressure. The crude was purified by silica gel flash column chromatography (0-8% MeOH in dichloromethane) to afford 26 mg (49%) of (S)-3-(3-(4-(5-amino-1,3,4-oxadiazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-isopropyloxazolidin-2-one. 1H NMR (400 MHz, DMSO-d6) δ 9.11 (d, 1H), 8.79 (s, 1H), 8.26 (d, 2H), 7.91 (d, 1H), 7.82 (d, 2H), 7.23 (s, 2H), 4.97 (m, 1H), 4.52 (d, 2H), 2.76 (m, 1H), 1.06 (d, 3H), 0.86 (d, 3H); LCMS (APCI+) m/z 406.4 [M+H]+.

Workup

  1. customwithin 3 minutes
  2. washthe organic layer was washed with water and brine
  3. dry with materialThe combined organic layers were dried over MgSO4
  4. concentrationconcentrated under reduced pressure
  5. customThe crude was purified by silica gel flash column chromatography (0-8% MeOH in dichloromethane)

Sources & evidence

ORD record
ord-83711893e9384ee4b9f5e7390eb474e0
Source dataset
uspto-grants-2014_10
Patent number
US08865726B2

Reaction notes

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