1H-1,2,4-Triazole → HCID 57822975, compound

HRID 2112523Notes

Reaction equation

HRID 2112523 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:14]2[CH:15]=[C:16]([F:21])[C:17]([O:19][CH3:20])=[CH:18][C:13]=2[NH:12][C:11](=[O:22])[CH2:10][N:9]=1.[CH2:23](N(C(C)C)C(C)C)C.N1C=NC=N1.P(Cl)(Cl)(Cl)=O>O1CCCC1>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:14]2[CH:15]=[C:16]([F:21])[C:17]([O:19][CH3:20])=[CH:18][C:13]=2[N:12]=[C:11]([O:22][CH3:23])[CH2:10][N:9]=1

Participants

6

Reactant 4

HCID 92571H-1,2,4-TriazoleHCID 24813Phosphorus oxychlorideHCID 81531DiisopropylethylamineHCID 57642349HCID 57642349, compound

Product 1

HCID 57822975HCID 57822975, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 3.0 g (0.0094 mole) of 5-(2-chlorophenyl)-1,3-dihydro-7-fluoro-8-methoxy-2H-1,4-benzodiazepin-2-one (Ia), 11.8 mL of ethyl diisopropyl amine, 4.62 g of 1,2,4-triazole and 45 mL of tetrahydrofuran at 0° C., was added 1.575 mL of phosphorous oxychloride. After 20 minutes, the cooling bath was removed, and the mixture was stirred at room temperature for another 60 minutes. Then, 17 mL of 4.37 M sodium methoxide in methanol solution was added to the reaction mixture. After stirring for 2 hours, another 5 mL of sodium methoxide solution was added, and the mixture stirred overnight. The mixture was then partitioned between ethyl acetate and water. The ethyl acetate layer was washed successively with water and brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to yield 3.2 g of 5-(2-chlorophenyl)-7-fluoro-2,8-dimethoxy-3H-1,4-benzodiazepine (intermediate Va), which was of sufficient purity to use in the next step.

Workup

  1. customthe cooling bath was removed
  2. additionThen, 17 mL of 4.37 M sodium methoxide in methanol solution was added to the reaction mixture
  3. stirringAfter stirring for 2 hours
  4. additionanother 5 mL of sodium methoxide solution was added
  5. stirringthe mixture stirred overnight
  6. customThe mixture was then partitioned between ethyl acetate and water
  7. washThe ethyl acetate layer was washed successively with water and brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-bce27ff688924d34b5e9d1e4376042b4
Source dataset
uspto-grants-2009_04
Patent number
US07524840B2

Reaction notes

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