Trifluoroacetic acid → 7-chloro-6-[3-(3,3-dimethyl-2-oxo-2,3-dihydro-1H-indol-5-yl)-propylthio]-2,3,4,5-tetrahydro-1H-benzo[d]azepine

HRID 2041606Notes

Reaction equation

HRID 2041606 reaction equation
FC(F)(F)C(O)=O.C(OC([N:15]1[CH2:21][CH2:20][C:19]2[C:22]([S:27][CH2:28][CH2:29][CH2:30][C:31]3[CH:32]=[C:33]4[C:37](=[CH:38][CH:39]=3)[NH:36][C:35](=[O:40])[C:34]4([CH3:42])[CH3:41])=[C:23]([Cl:26])[CH:24]=[CH:25][C:18]=2[CH2:17][CH2:16]1)=O)(C)(C)C>ClCCl>[Cl:26][C:23]1[CH:24]=[CH:25][C:18]2[CH2:17][CH2:16][NH:15][CH2:21][CH2:20][C:19]=2[C:22]=1[S:27][CH2:28][CH2:29][CH2:30][C:31]1[CH:32]=[C:33]2[C:37](=[CH:38][CH:39]=1)[NH:36][C:35](=[O:40])[C:34]2([CH3:42])[CH3:41]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 667073103-tert-butoxycarbonyl-7-chloro-6-[3-(3,3-dimethyl-2-oxo-2,3-dihydro-1H-indol-5-yl)-propylthio]-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Product 1

HCID 576566197-chloro-6-[3-(3,3-dimethyl-2-oxo-2,3-dihydro-1H-indol-5-yl)-propylthio]-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Add trifluoroacetic acid (0.2 mL, 2.6 mmol) to a solution of 3-tert-butoxycarbonyl-7-chloro-6-[3-(3,3-dimethyl-2-oxo-2,3-dihydro-1H-indol-5-yl)-propylthio]-2,3,4,5-tetrahydro-1H-benzo[d]azepine (257 mg, 0.5 mmol) in dichloromethane (5 mL) then stir at ambient temperature over the weekend. Concentrate in vacuo. Dissolve the residue in methanol and load onto an SCX column. Elute with methanol followed by 7M ammonia in methanol. Collect the basic fraction and concentrate in vacuo. Purify the residue by prep-LCMS [Supelco Discovery C18 column (21.2×100 mm, 5 μm packing), 25 mL/min flow rate, eluting with a water/acetonitrile gradient containing acetic acid as modifier over 12 min, fraction collection triggered by Electrospray MS] to give 7-chloro-6-[3-(3,3-dimethyl-2-oxo-2,3-dihydro-1H-indol-5-yl)-propylthio]-2,3,4,5-tetrahydro-1H-benzo[d]azepine as a white solid (101 mg, 25% over 2 steps). MS (ES+) m/z: 415 (M+H)+.

Workup

  1. concentrationConcentrate in vacuo
  2. dissolutionDissolve the residue in methanol
  3. washElute with methanol
  4. customCollect the basic fraction
  5. concentrationconcentrate in vacuo
  6. customPurify the residue by prep-LCMS [Supelco Discovery C18 column (21.2×100 mm, 5 μm packing), 25 mL/min flow rate
  7. washeluting with a water/acetonitrile gradient
  8. additioncontaining acetic acid as modifier over 12 min
  9. customfraction collection

Sources & evidence

ORD record
ord-3f0b497dfbb541ad8875b163eefebafc
Source dataset
uspto-grants-2013_11
Patent number
US08580780B2

Reaction notes

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