Bromochloromethane → HCID 86656549, compound

HRID 446851Notes

Reaction equation

HRID 446851 reaction equation
[CH2:1]([N:8]1[CH2:32][C@:31]2([C:33](O)=[O:34])[C@@H:10]([CH2:11][C@H:12]3[CH:25]4[C@@:16]([F:29])([C@:17]5([CH3:28])[C:22]([C@@H:23]([F:26])[CH2:24]4)=[CH:21][C:20](=[O:27])[CH:19]=[CH:18]5)[C@@H:15]([OH:30])[CH2:14][C@@:13]32[CH3:36])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1.[C:68](O)(=[S:70])C.C([O-])(=S)C.[K+].C([O-])(O)=O.[Na+].BrC[Cl:84]>CN(C=O)C>[Cl:84][CH2:68][S:70][C:33]([C@:31]12[C@@:13]3([CH3:36])[CH2:14][C@H:15]([OH:30])[C@@:16]4([F:29])[CH:25]([C@@H:12]3[CH2:11][C@H:10]1[CH2:9][N:8]([CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[CH2:32]2)[CH2:24][C@H:23]([F:26])[C:22]1[C@:17]4([CH3:28])[CH:18]=[CH:19][C:20](=[O:27])[CH:21]=1)=[O:34]

Participants

9

Reactant 7

HCID 6333BromochloromethaneHCID 79724-MethylmorpholineHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2×HCID 23670855Potassium ethanethioateHCID 67352569HCID 67352569, compoundHCID 178418634HCID 178418634, compound

Product 1

HCID 86656549HCID 86656549, compoundYield 11%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
70 °C

Procedure

A mixture of compound 93 (257 mg, 0.517 mmol), HATU (196 mg, 0.517 mmol) and N-methylmorpholine (56.8 μl, 0.517 mmol) in dry DMF (5 ml) is stirred at 70° C. under nitrogen for 1 hour. Further HATU (40 mg, 0.105 mmol) is added and the resulting mixture is stirred at 70° C. for 30 minutes. The solution is cooled to RT and it is poured into a solution of thioacetic acid (74.2 μl, 1.033 mmol) in dry DMF (2 ml). The resulting solution is stirred at RT under nitrogen for 2 hours. Potassium thioacetate (59.0 mg, 0.517 mmol) is added and the mixture is stirred at RT for 2 hours. NaHCO3 (87 mg, 1.033 mmol) and bromochloromethane (101 μl, 1.550 mmol) are added. The resulting mixture is stirred at RT under nitrogen overnight. The reaction mixture is partitioned between AcOEt and brine; the aqueous phase is extracted with AcOEt and the combined organic layers are washed with brine, dried over Na2SO4 and filtered. The solvent is evaporated and the crude is purified by silica gel chromatography (AcOEt/petroleum ether 3/7) to give a solid which is further triturated with petroleum ether to afford the title compound (32 mg, 10.9%).

Workup

  1. stirringthe resulting mixture is stirred at 70° C. for 30 minutes
  2. temperatureThe solution is cooled to RT
  3. stirringThe resulting solution is stirred at RT under nitrogen for 2 hours
  4. stirringthe mixture is stirred at RT for 2 hours
  5. stirringThe resulting mixture is stirred at RT under nitrogen overnight
  6. customThe reaction mixture is partitioned between AcOEt and brine
  7. extractionthe aqueous phase is extracted with AcOEt
  8. washthe combined organic layers are washed with brine
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. customThe solvent is evaporated
  12. customthe crude is purified by silica gel chromatography (AcOEt/petroleum ether 3/7)
  13. customto give a solid which
  14. customis further triturated with petroleum ether

Sources & evidence

ORD record
ord-b94125afcf694dffbfbf5fa6586b6758
Source dataset
uspto-grants-2013_07
Patent number
US08481517B2

Reaction notes

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