Trifluoroacetic acid → 6-(5-amino-[1,2,4]thiadiazol-3-ylthiomethyl)-7-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepine

HRID 1670571Notes

Reaction equation

HRID 1670571 reaction equation
[NH2:1][C:2]1[S:6][N:5]=[C:4]([S:7][CH2:8][C:9]2[C:19]3[CH2:18][CH2:17][N:16](C(OC(C)(C)C)=O)[CH2:15][CH2:14][C:13]=3[CH:12]=[CH:11][C:10]=2[Cl:27])[N:3]=1.FC(F)(F)C(O)=O>C(Cl)Cl>[NH2:1][C:2]1[S:6][N:5]=[C:4]([S:7][CH2:8][C:9]2[C:19]3[CH2:18][CH2:17][NH:16][CH2:15][CH2:14][C:13]=3[CH:12]=[CH:11][C:10]=2[Cl:27])[N:3]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 673359726-(5-amino-[1,2,4]thiadiazol-3-ylthiomethyl)-3-tert-butoxycarbonyl-7-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Product 1

HCID 598223046-(5-amino-[1,2,4]thiadiazol-3-ylthiomethyl)-7-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepineYield 72%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 6-(5-amino-[1,2,4]thiadiazol-3-ylthiomethyl)-3-tert-butoxycarbonyl-7-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.186 g, 0.436 mmol) in anhydrous DCM (10 mL) at room temperature add trifluoroacetic acid (10 mL) and stir the solution at room temperature overnight. Concentrate in vacuo and elute the residue through a SCX column (20 g). Dissolve the residue in DCM/methanol, add silica gel (5 g) and concentrate to a powder. Load the powder on to a dry column attached to a RediSep® column (40 g) and purify the crude mixture by preparative liquid chromatography (100:0 to 80:20 DCM/2M ammonia in methanol over 33 min; 80:20 DCM/2M ammonia in methanol over 33 min; 35 mL/min) to afford 6-(5-amino-[1,2,4]thiadiazol-3-ylthiomethyl)-7-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.102 g, 72%). MS (ES+) m/z: 327.1 (M+H)+.

Workup

  1. concentrationConcentrate in vacuo
  2. washelute the residue through a SCX column (20 g)
  3. dissolutionDissolve the residue in DCM/methanol
  4. additionadd silica gel (5 g)
  5. concentrationconcentrate to a powder
  6. custompurify the crude mixture by preparative liquid chromatography (100:0 to 80:20 DCM/2M ammonia in methanol over 33 min; 80:20 DCM/2M ammonia in methanol over 33 min; 35 mL/min)

Sources & evidence

ORD record
ord-abf4e6813c9644b0a9eca274b1f78b8a
Source dataset
uspto-grants-2011_08
Patent number
US07994163B2

Reaction notes

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