1,2-Dichloroethane → HCID 68522732, compound

HRID 1178887Notes

Reaction equation

HRID 1178887 reaction equation
[I-].[C:2]([NH:6][C:7]([C:9]1([CH:17]2[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]2)[CH2:15][CH:14]2[NH2+:16][CH:11]([CH2:12][CH2:13]2)[CH2:10]1)=[O:8])([CH3:5])([CH3:4])[CH3:3].[C:23]([N:27]1[CH2:32][CH2:31][C@@H:30]([C:33](O)=[O:34])[C@H:29]([C:36]2[CH:41]=[CH:40][C:39]([F:42])=[CH:38][C:37]=2[F:43])[CH2:28]1)([CH3:26])([CH3:25])[CH3:24].C1C=CC2N(O)N=NC=2C=1.C(Cl)C[Cl:56].CCN(C(C)C)C(C)C>ClCCl>[Cl-:56].[C:23]([NH+:27]1[CH2:32][CH2:31][C@@H:30]([C:33]([N:16]2[CH:11]3[CH2:12][CH2:13][CH:14]2[CH2:15][C:9]([C:7]([NH:6][C:2]([CH3:5])([CH3:3])[CH3:4])=[O:8])([CH:17]2[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]2)[CH2:10]3)=[O:34])[C@H:29]([C:36]2[CH:41]=[CH:40][C:39]([F:42])=[CH:38][C:37]=2[F:43])[CH2:28]1)([CH3:26])([CH3:24])[CH3:25]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 58780621HCID 58780621, compoundHCID 68527755HCID 68527755, compound

Product 1

HCID 68522732HCID 68522732, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 3-[(tert-butylamino)carbonyl]-3-cyclohexyl-8-azoniabicyclo[3.2.1]octane iodide (1-9) (42.0 mg, 0.100 mmol) in dichloromethane (5.0 mL) was added (3R,4R)-1-tert-butyl-3-(2,4-difluorophenyl)piperidine-4-carboxylic acid (1-12) (35.7 mg, 0.120 mmol), HOBt (16.2 mg, 0.120 mmol), EDC (23.0 mg, 0.120 mmol), and DIEA (38.8 mg, 0.300 mmol). The mixture was stirred at room temperature overnight, quenched with a saturated aqueous solution of NaHCO3, and extracted with dichloromethane (3×20 mL). The combined extracts were washed with brine, dried over anhydrous MgSO4, and concentrated. Purification of the crude residue by high-pressure liquid chromatography (gradient elution; 15%-95% acetonitrile/water as eluent) and addition of a solution of 1 N HCl solution in ether afforded (1-13) as a white solid (m/z (ES) 572 (MH+)).

Workup

  1. customquenched with a saturated aqueous solution of NaHCO3
  2. extractionextracted with dichloromethane (3×20 mL)
  3. washThe combined extracts were washed with brine
  4. dry with materialdried over anhydrous MgSO4
  5. concentrationconcentrated
  6. customPurification of the crude residue
  7. washby high-pressure liquid chromatography (gradient elution; 15%-95% acetonitrile/water as eluent) and addition of a solution of 1 N HCl solution in ether

Sources & evidence

ORD record
ord-28280601b4c44835ad97d9d9519d0f66
Source dataset
uspto-grants-2007_10
Patent number
US07276520B2

Reaction notes

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