Dimethylformamide → HCID 178433542, compound

HRID 1670555Notes

Reaction equation

HRID 1670555 reaction equation
C[N:2]1[CH:6]=[C:5]([SH:7])[N:4]=[C:3]1[CH3:8].[H-].[Na+].[C:11]([O:15][C:16]([N:18]1[CH2:24][CH2:23][C:22]2[C:25]([CH2:30]Cl)=[C:26]([Cl:29])[CH:27]=[CH:28][C:21]=2[CH2:20][CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12].[CH3:32]N(C=O)C>>[C:11]([O:15][C:16]([N:18]1[CH2:24][CH2:23][C:22]2[C:25]([CH:30]([S:7][C:5]3[N:4]=[C:3]([CH3:8])[NH:2][CH:6]=3)[CH3:32])=[C:26]([Cl:29])[CH:27]=[CH:28][C:21]=2[CH2:20][CH2:19]1)=[O:17])([CH3:14])([CH3:12])[CH3:13]

Participants

5

Reactant 4

HCID 6228Dimethylformamide2×HCID 24758Sodium hydrideHCID 21784407HCID 21784407, compoundHCID 597874103-tert-Butoxycarbonyl-7-chloro-6-chloromethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Product 1

HCID 178433542HCID 178433542, compoundYield 42%

Conditions

Temperature
45 °C

Procedure

Dissolve 1,2-dimethyl-1H-imidazole-4-thiol (450 mg, 1.8 mmol, prepared as described in J. Heterocyclic Chem. 1998, 35, 141) in anhydrous DMF (3 mL). Add sodium hydride (55 mg, 1.4 mmol, 60% dispersion in mineral oil) portionwise over 2 min at room temperature under a nitrogen atmosphere. Stir the yellow solution for 5 min, then add a solution of 3-tert-butoxycarbonyl-7-chloro-6-chloromethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine (300 mg, 0.9 mmol) in anhydrous DMF (3 mL) at room temperature over 2 min. Heat the mixture at 45° C. for 16 h under a nitrogen atmosphere. Cool the mixture to room temperature and quench with 10% aqueous sodium chloride (10 mL). Extract the mixture with EtOAc (2×30 mL). Dry the combined organic extracts over Na2SO4, filter and concentrate in vacuo. Purify the residue by chromatography on silica gel eluting with hexane/EtOAc (7:3 to 1:1 gradient) to obtain 3-tert-butoxycarbonyl-7-chloro-6-(1,2-dimethyl-1H-imidazol-4-ylthiomethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (160 mg, 42%). MS (ES+) m/z: 422.0 (M+H)+.

Workup

  1. temperatureCool the mixture to room temperature
  2. customquench with 10% aqueous sodium chloride (10 mL)
  3. extractionExtract the mixture with EtOAc (2×30 mL)
  4. dry with materialDry the combined organic extracts over Na2SO4
  5. filtrationfilter
  6. concentrationconcentrate in vacuo
  7. customPurify the residue by chromatography on silica gel eluting with hexane/EtOAc (7:3 to 1:1 gradient)

Sources & evidence

ORD record
ord-310cc264bdb44728907f9e852a706ccc
Source dataset
uspto-grants-2011_08
Patent number
US07994163B2

Reaction notes

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