Imidazole → HCID 86681237, compound

HRID 1848264Notes

Reaction equation

HRID 1848264 reaction equation
I[C:2]1[CH:28]=[CH:27][C:5]2[N:6]([CH2:9][C:10]3[CH:26]=[CH:25][C:13]4[N:14]=[C:15]([NH:17][C@@H:18]5[CH2:23][CH2:22][CH2:21][CH2:20][C@H:19]5[OH:24])[S:16][C:12]=4[CH:11]=3)[CH:7]=[N:8][C:4]=2[CH:3]=1.[NH:29]1[CH:33]=[CH:32][N:31]=[CH:30]1.C(=O)([O-])[O-].[K+].[K+].CN(C)[C@@H]1CCCC[C@H]1N>[Cu]I.CN(C=O)C>[N:29]1([C:2]2[CH:28]=[CH:27][C:5]3[N:6]([CH2:9][C:10]4[CH:26]=[CH:25][C:13]5[N:14]=[C:15]([NH:17][C@@H:18]6[CH2:23][CH2:22][CH2:21][CH2:20][C@H:19]6[OH:24])[S:16][C:12]=5[CH:11]=4)[CH:7]=[N:8][C:4]=3[CH:3]=2)[CH:33]=[CH:32][N:31]=[CH:30]1

Participants

7

Reactant 4

HCID 795ImidazoleHCID 11430Potassium CarbonateHCID 11275066(1R,2R)-N1,N1-Dimethylcyclohexane-1,2-diamineHCID 86681193HCID 86681193, compound

Product 1

HCID 86681237HCID 86681237, compoundYield 35.1%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

A stirred mixture of (1R,2R)-2-((6-((5-iodo-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (250 mg, 0.50 mmol) from Step 5 of Example 183, imidazole (80 mg, 1.18 mmol), potassium carbonate (82 mg, 0.59 mmol), trans-N,N-dimethylcyclohexane-1,2-diamine (9 mg, 0.063 mmol), copper (I) iodide (30 mg, 0.158 mmol) and DMF (2 mL) was heated at 120° C. for 3 h. The reaction mixture was cooled to rt and partitioned between EtOAc and water. The organic layer was separated, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography, eluting with 20:1 DCM: MeOH, to afford (1R,2R)-2-((6-((5-(1H-imidazol-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (78 mg, 35%) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 8.52 (s, 1H), 8.18 (s, 1H), 7.91-7.96 (m, 2H), 7.72-7.86 (m, 3H), 7.47 (dd, J=8.4, 1.8 Hz, 1H), 7.30 (d, J=8.1 Hz, 1H), 7.21 (dd, J=8.1, 1.5 Hz, 1H), 7.07 (d, J=1.2 Hz, 1H), 5.52 (s, 2H), 4.71 (d, J=5.1 Hz, 1H), 3.51 (m, 1H), 3.38 (m, 1H), 2.02 (m, 1H), 1.88 (m, 1H), 1.60-1.80 (m, 2H), 1.15-1.28 (m, 4H); LCMS (ESI) m/z 445 (M+H)+.

Workup

  1. temperatureThe reaction mixture was cooled to rt
  2. custompartitioned between EtOAc and water
  3. customThe organic layer was separated
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel flash chromatography
  8. washeluting with 20:1 DCM

Sources & evidence

ORD record
ord-1af218ce399043cbbef87f483bb8d206
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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