1,2-Dichloroethane → HCID 86629660, compound

HRID 911553Notes

Reaction equation

HRID 911553 reaction equation
[F:1][C:2]([F:13])([F:12])[C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=O)=[CH:5][CH:4]=1.C(Cl)CCl.ON1C2C=CC=CC=2N=N1.[NH2:28][CH2:29][CH2:30][CH2:31][S:32][C:33]1[C:43]2[CH2:42][CH2:41][N:40](C(OC(C)(C)C)=O)[CH2:39][CH2:38][C:37]=2[CH:36]=[CH:35][C:34]=1[Cl:51].[F:52][C:53]([F:58])([F:57])[C:54]([OH:56])=[O:55]>CN(C=O)C.CN(C)C1C=CN=CC=1.C(Cl)Cl>[F:52][C:53]([F:58])([F:57])[C:54]([OH:56])=[O:55].[Cl:51][C:34]1[CH:35]=[CH:36][C:37]2[CH2:38][CH2:39][NH:40][CH2:41][CH2:42][C:43]=2[C:33]=1[S:32][CH2:31][CH2:30][CH2:29][NH:28][C:7](=[O:9])[C:6]1[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:13])[F:12])=[CH:11][CH:10]=1

Participants

9

Reactant 5

HCID 111,2-DichloroethaneHCID 6422Trifluoroacetic acidHCID 99664-(Trifluoromethyl)benzoic acidHCID 757711-HydroxybenzotriazoleHCID 57656177HCID 57656177, compound

Product 1

HCID 86629660HCID 86629660, compoundYield 18%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of 4-trifluoromethylbenzoic acid (60.0 mg, 0.316 mmol) in anhydrous DMF (1.2 mL) at ambient temperature under nitrogen, add EDC (63.6 mg, 0.332 mmol), 1-hydroxybenzotriazole (44.8 mg, 0.332 mmol), 4-dimethylaminopyridine (40.5 mg, 0.332 mmol) and a solution of 6-(3-aminopropylthio)-3-tert-butoxycarbonyl-7-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepine (123 mg, 0.332 mmol) in DCM (2 mL). Stir for 18 h at ambient temperature. Add water, extract twice with EtOAc, dry over anhydrous Na2SO4, and concentrate in vacuo. Treat the residue with trifluoroacetic acid (0.272 mL, 0.640 mmol) in DCM (0.451 mL) at ambient temperature for 18 h. Concentrate in vacuo and purify by preparative reverse phase 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 as a white solid (31.0 mg, 18%). MS (APCI+) m/z 443 (M+H)+.

Workup

  1. extractionAdd water, extract twice with EtOAc
  2. dry with materialdry over anhydrous Na2SO4
  3. concentrationconcentrate in vacuo
  4. concentrationConcentrate in vacuo
  5. custompurify by preparative reverse phase HPLC [Column

Sources & evidence

ORD record
ord-6a916d00e31a4460bea490fae0c9481f
Source dataset
uspto-grants-2011_09
Patent number
US08022062B2

Reaction notes

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