1,2-Dichloroethane → HCID 178484580, compound

HRID 1183205Notes

Reaction equation

HRID 1183205 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([S:8][C:9]2[NH:13][CH:12]=[N:11][C:10]=2[C:14]2[CH:19]=[CH:18][C:17]([C@H:20]3[CH2:22][C@@H:21]3[C:23](O)=[O:24])=[CH:16][CH:15]=2)=[N:6][CH:7]=1.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.C[CH2:41][N:42](C(C)C)[CH:43](C)C.CNC>CN(C=O)C.CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([S:8][C:9]2[NH:13][CH:12]=[N:11][C:10]=2[C:14]2[CH:19]=[CH:18][C:17]([C@H:20]3[CH2:22][C@@H:21]3[C:23]([N:42]([CH3:43])[CH3:41])=[O:24])=[CH:16][CH:15]=2)=[N:6][CH:7]=1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 674DimethylamineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 178525788HCID 178525788, compound

Product 1

HCID 178484580HCID 178484580, compoundYield 79.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

(1S,2S)-2-(4-{5-[(5-chloropyridin-2-yl)thio]-1H-imidazol-4-yl}phenyl)cyclopropanecarboxylic acid (Step 3 product, 73 mg, 0.196 mmol), HOBT (60 mg, 0.393 mmol), and EDC (113 mg, 0.589 mmol) were dissolved in 3 mL of DMF, to which were added Hunig's base (0.206 mL, 1.178 mmol) and dimethyl amine (2 M THF solution, 0.294 mL, 0.589 mmol). The reaction was heated at 80° C. for 30-60 min. Upon cooling to rt, the reaction was diluted with EtOAc (80 mL), and the reaction mixture was washed with water (2-3 times) and brine, dried, and concentrated to dryness. The residue was purified by silica column (80-100% EtOAc in hexanes) to give 62 mg (79%) of the title compound. 1H NMR (500 MHz, (CD3OD): 8.38 (s, 1H), 7.97 (s, 1H), 7.65 (d, 2H), 7.59 (d, 1H), 7.18 (d, 2H), 6.82 (d, 1H), 3.16 (s, 3H), 2.97 (s, 3H), 2.38 (m, 1H), 2.19 (m, 1H), 1.54 (m, 1H), 1.27 (m, 1H). LCMS: m/z 399 (M+H)+. Human FAAH lysate assay: IC50=649.6 nM.

Workup

  1. temperatureUpon cooling to rt
  2. washthe reaction mixture was washed with water (2-3 times) and brine
  3. customdried
  4. concentrationconcentrated to dryness
  5. customThe residue was purified by silica column (80-100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-ff01f6bd3ead4e22931f9a9fff7a9acd
Source dataset
uspto-grants-2014_03
Patent number
US08664253B2

Reaction notes

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