Potassium Sodium Tartrate → HCID 178444049, compound

HRID 923585Notes

Reaction equation

HRID 923585 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[NH2:10])[C:5]#[N:6].C[Al](C)C.[CH2:15]([O:22][C:23]1[CH:28]=[CH:27][C:26]([CH2:29][C:30](OC)=O)=[CH:25][CH:24]=1)[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21].[C@H](O)(C([O-])=O)[C@@H](O)C([O-])=O.[Na+].[K+]>C1COCC1.O.CC(=O)OCC>[CH2:15]([O:22][C:23]1[CH:28]=[CH:27][C:26]([CH2:29][C:30]2[NH:10][C:9]3[CH:8]=[CH:7][C:4]([C:5]#[N:6])=[CH:3][C:2]=3[N:1]=2)=[CH:25][CH:24]=1)[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21]

Participants

8

Reactant 4

HCID 9357Potassium Sodium TartrateHCID 7372853,4-DiaminobenzonitrileHCID 16682925TrimethylaluminumHCID 71076749HCID 71076749, compound

Product 1

HCID 178444049HCID 178444049, compoundYield 78%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
60 °C

Procedure

To a stirred solution of 3,4-diaminobenzonitrile (1.08 g, 8.10 mmol) in THF (20 mL) at 0° C. was added trimethylaluminum (4.86 mL, 9.72 mmol, 2 M in hexanes). After 10 min, methyl 2-(4-(heptyloxy)phenyl)acetate (2.36 g, 8.91 mmol) was added and the cooling bath removed. After stirring for 48 h at 60° C., the reaction mixture was allowed to cool to room temperature then poured into a mixture of Rochelle's salt (6.86 g, 24.31 mmol) in water (150 mL) and EA (100 mL) and stirred for 2 h. The layers were split and the aqueous layer further extracted with EA (50 mL). The combined organics were washed successively with water (100 mL) and brine (50 mL), dried over MgSO4 and evaporated. The residue was taken up in xylenes (50 mL), treated with toxic acid (0.154 g, 0.810 mmol) and heated under reflux for 18 h. The reaction mixture was allowed to cool, diluted with EA (100 mL), washed with NaHCO3 (100 mL), dried over MgSO4 and evaporated. The crude material was purified by chromatography (EA/isohexanes) then re-slurried from isohexanes to afford 2.19 g, (78%) of 2-(4-(heptyloxy)benzyl)-1H-benzo[d]imidazole-5-carbonitrile as a white solid INT-46. LCMS-ESI (m/z) calculated for C22H25N3O: 347; found 348 [M+H]+, tR=2.82 min (Method 5).

Workup

  1. customthe cooling bath removed
  2. temperatureto cool to room temperature
  3. stirringstirred for 2 h
  4. customThe layers were split
  5. extractionthe aqueous layer further extracted with EA (50 mL)
  6. washThe combined organics were washed successively with water (100 mL) and brine (50 mL)
  7. dry with materialdried over MgSO4
  8. customevaporated
  9. temperatureheated
  10. temperatureunder reflux for 18 h
  11. temperatureto cool
  12. washwashed with NaHCO3 (100 mL)
  13. dry with materialdried over MgSO4
  14. customevaporated
  15. customThe crude material was purified by chromatography (EA/isohexanes)

Sources & evidence

ORD record
ord-82bf18bc1a914725b82d20c602facde5
Source dataset
uspto-grants-2016_03
Patent number
US09278910B2

Reaction notes

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