Pyridine → HCID 59003110, compound

HRID 2353951Notes

Reaction equation

HRID 2353951 reaction equation
[C:1](Cl)(=[O:3])[CH3:2].[CH:5]([O:8][C:9]([N:11]1[CH2:17][CH2:16][CH2:15][CH:14]([NH:18][CH2:19][C:20]2[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[C:22]([C:30]([F:33])([F:32])[F:31])[CH:21]=2)[C:13]2[CH:34]=[CH:35][C:36]([Cl:39])=[C:37]([CH3:38])[C:12]1=2)=[O:10])([CH3:7])[CH3:6].N1C=CC=CC=1>ClCCl>[CH:5]([O:8][C:9]([N:11]1[CH2:17][CH2:16][CH2:15][CH:14]([N:18]([C:1](=[O:3])[CH3:2])[CH2:19][C:20]2[CH:21]=[C:22]([C:30]([F:33])([F:31])[F:32])[CH:23]=[C:24]([C:26]([F:28])([F:29])[F:27])[CH:25]=2)[C:13]2[CH:34]=[CH:35][C:36]([Cl:39])=[C:37]([CH3:38])[C:12]1=2)=[O:10])([CH3:7])[CH3:6]

Participants

5

Reactant 3

HCID 1049PyridineHCID 6367Acetyl chlorideHCID 86616078HCID 86616078, compound

Product 1

HCID 59003110HCID 59003110, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Inject titanium isopropoxide (0.176 mL, 0.60 mmol) to a mixture of 8-chloro-9-methyl-5-oxo-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid isopropyl ester (90 mg, 0.30 mmol) and 3,5-bis(trifluoromethyl)benzylamine (137 mg, 0.45 mmol) at room temperature under an atmosphere of nitrogen and stir the solution for 14 h. Add methanol (1.3 mL) and sodium borohydride (28 mg, 0.75 mmol) and stir the mixture under nitrogen at room temperature for 2 h. Add 0.1M NaOH, stir for 30 min. Filter through celite and wash the residue with AcOEt. Separate organic layer, extract aqueous with AcOEt. Wash organic layer with brine and dry the organic layers over anhydrous sodium sulfate. Filter and remove the solvent under reduced pressure. Purify the residue by flash chromatography, eluting with hexanes/ethyl acetate, to afford (+/−)-5-(3,5-Bis-trifluoromethyl-benzylamino)-8-chloro-9-methyl-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid isopropyl ester (90 mg, 57%). Add acetyl chloride (0.025 mL, 0.34 mmol) dropwise to a solution of the amine (90 mg, 0.17 mmol) and pyridine (0.025 mL, 0.34 mmol) in dichloromethane (1.2 mL) at 0° C. Stir under nitrogen at room temperature for 1 h 30 min. Add water and extract with dichloromethane. Dry the organic layer over anhydrous magnesium sulfate, filter and remove the solvent under reduced pressure. Purify the residue by flash chromatography, eluting with hexanes/ethyl acetate, to afford the title compound (40 mg, 42%); MS (ES+): 565 (M+H).

Workup

  1. customat 0° C
  2. extractionAdd water and extract with dichloromethane
  3. dry with materialDry the organic layer over anhydrous magnesium sulfate
  4. filtrationfilter
  5. customremove the solvent under reduced pressure
  6. customPurify the residue by flash chromatography
  7. washeluting with hexanes/ethyl acetate

Sources & evidence

ORD record
ord-a067cb9bf6f94283a424b4e9bfcdd0e4
Source dataset
uspto-grants-2010_07
Patent number
US07749992B2

Reaction notes

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