Trifluoroacetic acid → HCID 66707120, compound

HRID 2041423Notes

Reaction equation

HRID 2041423 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][S:5][C:6]1[C:16]2[CH2:15][CH2:14][N:13](C(OC(C)(C)C)=O)[CH2:12][CH2:11][C:10]=2[CH:9]=[CH:8][C:7]=1[Cl:24].C(N(CC)CC)C.[C:32](Cl)(=[O:39])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.[F:41][C:42]([F:47])([F:46])[C:43]([OH:45])=[O:44]>C(Cl)Cl>[F:41][C:42]([F:47])([F:46])[C:43]([OH:45])=[O:44].[C:32]([NH:1][CH2:2][CH2:3][CH2:4][S:5][C:6]1[C:16]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11][C:10]=2[CH:9]=[CH:8][C:7]=1[Cl:24])(=[O:39])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 7412Benzoyl chlorideHCID 8471TriethylamineHCID 57656177HCID 57656177, compound

Product 1

HCID 66707120HCID 66707120, compoundYield 12%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 6-(3-aminopropylthio)-3-tert-butoxycarbonyl-7-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepine (46.7 mg, 0.126 mmol) in dry DCM (0.5 mL) at ambient temperature under nitrogen, add triethylamine (19.3 μL, 0.139 mmol) and benzoyl chloride (16.1 μL, 0.139 mmol). Stir at ambient temperature for 2.5 h. Add aqueous saturated ammonium chloride and water, extract three times with EtOAc, dry over anhydrous Na2SO4, and concentrate in vacuo. Dissolve the residue in DCM (0.16 mL), add trifluoroacetic acid (44.6 μL, 0.58 mmol) and stir for 18 h at ambient temperature. Concentrate in vacuo and purify by preparative HPLC [Column: YMC ODS-AQ 120 Å 20×250 mm [S10-20 μm]; eluent: 95:5 to 5:95 A/B; solvent A: water, 0.1% TFA, 1% isopropanol; solvent B: acetonitrile, 0.05% TFA, 1% isopropanol; flow rate 20 mL/min] to give the title compound (7.0 mg, 12%). MS (APCI+) m/z 375 (M+H)+.

Workup

  1. extractionAdd aqueous saturated ammonium chloride and water, extract three times with EtOAc
  2. dry with materialdry over anhydrous Na2SO4
  3. concentrationconcentrate in vacuo
  4. dissolutionDissolve the residue in DCM (0.16 mL)
  5. stirringstir for 18 h at ambient temperature
  6. concentrationConcentrate in vacuo
  7. custompurify by preparative HPLC [Column

Sources & evidence

ORD record
ord-bd233af5d9c942ffb6a395f530e625ef
Source dataset
uspto-grants-2013_11
Patent number
US08580780B2

Reaction notes

Loading…