Triethylamine → HCID 46852752, compound

HRID 1402744Notes

Reaction equation

HRID 1402744 reaction equation
[N:1]1([C:6]2[CH:14]=[CH:13][C:9]([C:10]([OH:12])=O)=[CH:8][CH:7]=2)[CH:5]=[CH:4][N:3]=[CH:2]1.C(Cl)(=O)C(Cl)=O.C(N(CC)CC)C.[NH:28]1[CH2:31][CH:30]([C:32]([N:34]2[CH2:40][CH2:39][CH2:38][N:37]([CH:41]3[CH2:44][CH2:43][CH2:42]3)[CH2:36][CH2:35]2)=[O:33])[CH2:29]1>ClCCl.CN(C=O)C>[CH:41]1([N:37]2[CH2:38][CH2:39][CH2:40][N:34]([C:32]([CH:30]3[CH2:29][N:28]([C:10]([C:9]4[CH:8]=[CH:7][C:6]([N:1]5[CH:5]=[CH:4][N:3]=[CH:2]5)=[CH:14][CH:13]=4)=[O:12])[CH2:31]3)=[O:33])[CH2:35][CH2:36]2)[CH2:44][CH2:43][CH2:42]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 7365294-(1-Imidazolyl)benzoic AcidHCID 667393581-(Azetidin-3-ylcarbonyl)-4-cyclobutyl-1,4-diazepane

Product 1

HCID 46852752HCID 46852752, compoundYield 4.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 4-(1H-imidazol-1-yl)benzoic acid (150 mg, 0.80 mmol) in dichloromethane (10 mL) cooled to 0° C. was added oxalyl chloride (1 mL). DMF (2 drops) was added and the mixture was stirred for 45 min at 0° C. and volatiles were then removed at reduced pressure. The residue was diluted with dichloromethane (20 mL), cooled to 0° C. and triethylamine (201 mg, 2.0 mmol) was added followed by 1-(azetidin-3-ylcarbonyl)-4-cyclobutyl-1,4-diazepane (187 mg, 0.79 mmol). The resulting mixture was stirred at RT for 16 h before being diluted with more dichloromethane (50 mL) and quenched by addition of water (50 mL). The organic layer was then washed with saturated aqueous NaHCO3 (50 mL), dried (Na2SO4), filtered and concentrated at reduced pressure. Purification by silica FCC (using a gradient of eluents; 97:3 to 95:5 DCM/2M NH3 in MeOH) followed by purification by preparative HPLC (Method 2) gave the title compound (14 mg, 4% yield) as pale yellow oil.

Workup

  1. customvolatiles were then removed at reduced pressure
  2. additionThe residue was diluted with dichloromethane (20 mL)
  3. temperaturecooled to 0° C.
  4. stirringThe resulting mixture was stirred at RT for 16 h
  5. customquenched by addition of water (50 mL)
  6. washThe organic layer was then washed with saturated aqueous NaHCO3 (50 mL)
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated at reduced pressure
  10. customPurification by silica FCC (
  11. custom97:3 to 95:5 DCM/2M NH3 in MeOH) followed by purification by preparative HPLC (Method 2)

Sources & evidence

ORD record
ord-cdcf36ae8abd465794dd8bb9f6868419
Source dataset
uspto-grants-2014_12
Patent number
US08912176B2

Reaction notes

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