2,4,6-Triisopropylbenzenesulfonyl azide → 3-Azido-2,4-dioxo-1,5-bis-(cyclopropylmethyl)-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine

HRID 965769Notes

Reaction equation

HRID 965769 reaction equation
[O:1]=[C:2]1[N:8]([CH2:9][CH:10]2[CH2:12][CH2:11]2)[C:7]2[CH:13]=[CH:14][CH:15]=[CH:16][C:6]=2[N:5]([CH2:17][CH:18]2[CH2:20][CH2:19]2)[C:4](=[O:21])[CH2:3]1.CC(C1C=C(C(C)C)C(S([N:37]=[N+:38]=[N-:39])(=O)=O)=C(C(C)C)C=1)C>C1COCC1>[N:37]([CH:3]1[C:4](=[O:21])[N:5]([CH2:17][CH:18]2[CH2:19][CH2:20]2)[C:6]2[CH:16]=[CH:15][CH:14]=[CH:13][C:7]=2[N:8]([CH2:9][CH:10]2[CH2:11][CH2:12]2)[C:2]1=[O:1])=[N+:38]=[N-:39]

Participants

4

Reactant 2

HCID 3717072,4,6-Triisopropylbenzenesulfonyl azideHCID 223124822,4-Dioxo-1,5-bis-(cyclopropylmethyl)-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine

Product 1

HCID 223122573-Azido-2,4-dioxo-1,5-bis-(cyclopropylmethyl)-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-30 °C

Procedure

For this substrate General Procedure 8-K was modified in the following manner. Initially the product from Step A was suspended (not a solution) in THF at −78° C., and following addition of the KN(TMS)2 solution, this suspension was allowed to warm to −30° C., during which the suspension became a solution, and was re-cooled to −78° C. Upon re-cooling to −78° C. a precipitate began to form, therefore the reaction flask containing the mixture was partially raised above the cooling bath until the internal temperature rose to −50° C.; then the trisyl azide solution was added. The cooling bath was removed and the mixture allowed to warm to −20° C. whereupon the mixture had become a nearly homogenous solution, and the AcOH was added. Then, treated as described in the general procedure. 3-Azido-2,4-dioxo-1,5-bis-(cyclopropylmethyl)-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine was purified by trituration with hot to room temperature EtOAc, followed by recrystalization from hot to −23° C. CHCl3/EtOAc/EtOH (5:5:1) and isolated as a white solid.

Workup

  1. customat −78° C.
  2. temperaturewas re-cooled to −78° C
  3. temperatureUpon re-cooling to −78° C. a precipitate
  4. customto form
  5. additionthe reaction flask containing the mixture
  6. temperaturewas partially raised above the cooling bath until the internal temperature
  7. customrose to −50° C.
  8. customThe cooling bath was removed
  9. temperatureto warm to −20° C. whereupon the mixture
  10. additionthe AcOH was added
  11. additionThen, treated
  12. custom3-Azido-2,4-dioxo-1,5-bis-(cyclopropylmethyl)-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine was purified by trituration with hot to room temperature EtOAc
  13. customfollowed by recrystalization from hot to −23° C
  14. customCHCl3/EtOAc/EtOH (5:5:1) and isolated as a white solid

Sources & evidence

ORD record
ord-5e01309d6cb646188040724706458702
Source dataset
uspto-grants-2005_10
Patent number
US06951854B1

Reaction notes

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