Pyridine → HCID 86761167, compound

HRID 507163Notes

Reaction equation

HRID 507163 reaction equation
[F:1][C:2]([F:39])([F:38])[C:3]1[CH:4]=[C:5]([CH:31]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:33]=1)[CH2:6][N:7]([C@H:14]1[CH2:20][CH2:19][CH2:18][NH:17][C:16]2[C:21]([CH3:30])=[C:22]([C:26]([F:29])([F:28])[F:27])[C:23]([CH3:25])=[CH:24][C:15]1=2)[C:8]1[N:9]=[N:10][N:11]([CH3:13])[N:12]=1.N1C=CC=CC=1.[CH3:46][O:47][C:48](=[O:52])[C:49](Cl)=[O:50]>ClCCl>[CH3:46][O:47][C:48](=[O:52])[C:49]([N:17]1[CH2:18][CH2:19][CH2:20][C@H:14]([N:7]([CH2:6][C:5]2[CH:31]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:33]=[C:3]([C:2]([F:1])([F:38])[F:39])[CH:4]=2)[C:8]2[N:9]=[N:10][N:11]([CH3:13])[N:12]=2)[C:15]2[CH:24]=[C:23]([CH3:25])[C:22]([C:26]([F:27])([F:28])[F:29])=[C:21]([CH3:30])[C:16]1=2)=[O:50]

Participants

5

Reactant 3

HCID 1049PyridineHCID 79846Methyl chloroglyoxylateHCID 59432300HCID 59432300, compound

Product 1

HCID 86761167HCID 86761167, compoundYield 81.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Dissolve (S)-(3,5-Bis-trifluoromethyl-benzyl)-(7,9-dimethyl-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl)-(2-methyl-2H-tetrazol-5-yl)-amine (Example 148, Step 2) (0.200 g, 0.353 mmol) in dichloromethane (4 mL), cool the solution down with an ice-water bath. Add pyridine (0.143 mL, 1.77 mmol) followed by chloro-oxo-acetic acid methyl ester (0.162 mL, 1.77 mmol) dropwise. Warm up the reaction to room temperature and stir overnight. Dilute the reaction mixture with more dichloromethane (10 mL), and wash with aqueous NaHCO3 (10 mL). Extract back the aqueous layer with dichloromethane (10 mL). Combine the organic layers, dry over anhydrous sodium sulfate and filter. Remove the solvent under reduced pressure. Chromatograph the residue over silica gel, eluting with ethyl acetate/hexanes (0-30%), to provide the title compound (0.187 g, 81%). MS (ES+): 653 (M+H).

Workup

  1. temperaturecool the solution down with an ice-water bath
  2. temperatureWarm up
  3. customthe reaction to room temperature
  4. washwash with aqueous NaHCO3 (10 mL)
  5. extractionExtract back the aqueous layer with dichloromethane (10 mL)
  6. dry with materialCombine the organic layers, dry over anhydrous sodium sulfate
  7. filtrationfilter
  8. customRemove the solvent under reduced pressure
  9. washChromatograph the residue over silica gel, eluting with ethyl acetate/hexanes (0-30%)

Sources & evidence

ORD record
ord-ea2e2bf14a604fd9a4c6252a0dc4b8d2
Source dataset
uspto-grants-2010_08
Patent number
US07786108B2

Reaction notes

Loading…