Trifluoroacetic acid → HCID 66707120, compound

HRID 911552Notes

Reaction equation

HRID 911552 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-d50c800b22d74fc5a28c805b010f518d
Source dataset
uspto-grants-2011_09
Patent number
US08022062B2

Reaction notes

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