HCID 10224027, compound → HCID 11531936, compound

HRID 1786445Notes

Reaction equation

HRID 1786445 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:10]2[N:11]([CH3:25])[C:12]([S:15][CH2:16][CH2:17][CH2:18][N:19]3[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]3)=[N:13][CH:14]=2)=[O:9])=[CH:4][CH:3]=1>O=[Mn]=O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:10]2[N:11]([CH3:25])[C:12]([S:15][CH2:16][CH2:17][CH2:18][N:19]3[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]3)=[N:13][CH:14]=2)[OH:9])=[CH:4][CH:3]=1

Participants

3

Reactant 1

HCID 10224027HCID 10224027, compound

Product 1

HCID 11531936HCID 11531936, compoundYield 20%

Reagents, catalysts & solvents 1

HCID 14801Manganese dioxideCatalyst

Procedure

The product of Example III, Step B (0.11 g) in acetone (5 mL) and DMF (5 mL) was treated with piperidine (0.22 g) and K2CO3 (1.8 g). The reaction mixture was allowed to stir for 16 h and then partitioned between EtOAc (75 mL) and aqueous (aq.) saturated (satd.) NaHCO3 (50 mL). The organic portion was washed with brine (50 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel using 2-5% MeOH/CH2Cl2 as the eluent to provide the title compound (0.27 g, 55%). M calc=423; M+H found=424. Step D: (4-Bromophenyl)-[3-methyl-2-(3-piperidin-1-yl-propylsulfanyl)-3H-imidazol-4-yl]-methanone. The product from Example III, Step C (0.05 g) was subjected to the same conditions described in Example I, Step C (MnO2, 0.05g) to provide the title compound (0.01 g, 20%). M calc=421; M+H found=422. 1H NMR (400 MHz, CDCl3): δ 7.65 (dd, J=8.6, 2.0 Hz, 2H), 7.55 (dd, J=8.6, 2.0 Hz, 2H), 7.46 (s, 1H), 3.86 (s, 3H), 3.28 (t, J=7.1 Hz, 2H), 2.36 (tm, J=7.0 Hz, 6H), 1.91 (m, 2H), 1.55 (m, 4H), 1.40 (br m, 2H). The compound demonstrated useful biological activity when assessed with a [3H]—N-methylhistamine binding assay (see Table in Example XXV). Step E: Additional compounds prepared following Scheme I, and Example III, Steps A, B, C, and D. The following compounds of formula (I) were prepared following Scheme I and Example III, Steps A, B, C, and D; and substituting reagents, and adjusting reaction conditions as needed. The compounds were found to have useful biological activity based on the Ki (nM) value from a [3H]-N-methylhistamine binding assay.

Sources & evidence

ORD record
ord-11ad7b5b2b0443ce966e181291007d7a
Source dataset
uspto-grants-2009_03
Patent number
US07507756B2

Reaction notes

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