Triethylamine → HCID 86681233, compound

HRID 1848260Notes

Reaction equation

HRID 1848260 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.[C:29]([O:33][CH2:34][CH3:35])(=[O:32])[CH:30]=[CH2:31].C(N(CC)CC)C>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[OH:24][C@@H:19]1[CH2:20][CH2:21][CH2:22][CH2:23][C@H:18]1[NH:17][C:15]1[S:16][C:12]2[CH:11]=[C:10]([CH2:9][N:6]3[C:5]4[CH:27]=[CH:28][C:2](/[CH:31]=[CH:30]/[C:29]([O:33][CH2:34][CH3:35])=[O:32])=[CH:3][C:4]=4[N:8]=[CH:7]3)[CH:26]=[CH:25][C:13]=2[N:14]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 8821Ethyl AcrylateHCID 86681193HCID 86681193, compound

Product 1

HCID 86681233HCID 86681233, compoundYield 130.8%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

To a stirred solution of (1R,2R)-2-((6-((5-iodo-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (150 mg, 0.30 mmol) from Step 5 of Example 183 in DMF (2 mL) were added ethyl acrylate (0.036 mL, 0.33 mmol), palladium (II) acetate (7 mg 0.03 mmol), and triethylamine (0.088 mL, 0.63 mmol). The mixture was flushed with argon and heated in a sealed vessel at 120° C. for 3 h. The mixture was cooled to rt and partitioned between EtOAc and water. The separated aqueous layer was extracted twice with EtOAc and the combined organic phases were washed three times with a 1:1 mixture of water and brine, dried over MgSO4, filtered, and concentrated under reduced pressure to afford (E)-ethyl 3-(1-((2-(((1R,2R)-2-hydroxycyclohexyl)amino)benzo[d]thiazol-6-yl)methyl)-1H-benzo[d]imidazol-5-yl)acrylate (187 mg) as a solid. The product was used directly in the next step. LCMS (ESI) m/z 477 (M+H)+.

Workup

  1. customThe mixture was flushed with argon
  2. temperatureThe mixture was cooled to rt
  3. custompartitioned between EtOAc and water
  4. extractionThe separated aqueous layer was extracted twice with EtOAc
  5. washthe combined organic phases were washed three times
  6. additionwith a 1:1 mixture of water and brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-b04aace9fe1942debfd572ce2d86aace
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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