Hydrochloric Acid → (+/-)-isopropyl 5-[(3,5-bistrifluoromethyl-benzyl)-(1H-tetrazol-5-yl)-amino]-8-chloro-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate

HRID 507061Notes

Reaction equation

HRID 507061 reaction equation
[N:1]([Sn](CCCC)(CCCC)CCCC)=[N+:2]=[N-:3].[F:17][C:18]([F:52])([F:51])[C:19]1[CH:20]=[C:21]([CH:44]=[C:45]([C:47]([F:50])([F:49])[F:48])[CH:46]=1)[CH2:22][N:23]([C:42]#[N:43])[CH:24]1[CH2:30][CH2:29][CH2:28][N:27]([C:31]([O:33][CH:34]([CH3:36])[CH3:35])=[O:32])[C:26]2[CH:37]=[C:38]([Cl:41])[CH:39]=[CH:40][C:25]1=2.C(OCC)(=O)C.Cl>C1(C)C=CC=CC=1>[F:50][C:47]([F:48])([F:49])[C:45]1[CH:44]=[C:21]([CH:20]=[C:19]([C:18]([F:17])([F:51])[F:52])[CH:46]=1)[CH2:22][N:23]([C:42]1[NH:3][N:2]=[N:1][N:43]=1)[CH:24]1[CH2:30][CH2:29][CH2:28][N:27]([C:31]([O:33][CH:34]([CH3:36])[CH3:35])=[O:32])[C:26]2[CH:37]=[C:38]([Cl:41])[CH:39]=[CH:40][C:25]1=2

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 4984872Tributyltin azideHCID 59432310(+/-)-Isopropyl 5-[(3,5-bistrifluoromethyl-benzyl)-cyano-amino]-8-chloro-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate

Product 1

HCID 178459687(+/-)-isopropyl 5-[(3,5-bistrifluoromethyl-benzyl)-(1H-tetrazol-5-yl)-amino]-8-chloro-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

Add azidotributyltin (0.19 mL, 0.68 mmol) to a solution of (+/−)-isopropyl 5-[(3,5-bistrifluoromethyl-benzyl)-cyano-amino]-8-chloro-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate (180 mg, 0.34 mmol) in toluene (3.6 mL). Stir the mixture at 80° C. overnight. Cool down the mixture to room temperature; add ethyl acetate and 1N HCl (8.2 mL) and stir at room temperature for 1 h. Separate the layers, wash the organic phase with saturated KF, then with brine, dry over anhydrous sodium sulfate, filter and remove the solvent under reduced pressure. Purify the residue by flash chromatography, eluting with dichloromethane/methanol, and then by reverse phase purification to provide 198 mg (quantitative) of the title compound. MS (ES−): 575 (M−H).

Workup

  1. temperatureCool down the mixture to room temperature
  2. customSeparate the layers
  3. washwash the organic phase with saturated KF
  4. dry with materialwith brine, dry over anhydrous sodium sulfate
  5. filtrationfilter
  6. customremove the solvent under reduced pressure
  7. customPurify the residue by flash chromatography
  8. washeluting with dichloromethane/methanol
  9. customby reverse phase purification

Sources & evidence

ORD record
ord-bcc3c94c2e4540ae9cd0ac612045a6ef
Source dataset
uspto-grants-2010_08
Patent number
US07786108B2

Reaction notes

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