Imidazole → HCID 59200399, compound

HRID 1685288Notes

Reaction equation

HRID 1685288 reaction equation
[S:1]1[CH:5]=[CH:4][N:3]=[C:2]1[NH:6][C:7]1[CH:8]=[C:9]([CH:14]=[CH:15][N:16]=1)[C:10]([O:12]C)=O.[H-].[Al+3].[Li+].[H-].[H-].[H-].[OH-].[Na+].N1C=CN=C1.[Si:30](Cl)([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31]>O1CCCC1.CN(C)C=O.ClCCl.O>[Si:30]([O:12][CH2:10][C:9]1[CH:14]=[CH:15][N:16]=[C:7]([NH:6][C:2]2[S:1][CH:5]=[CH:4][N:3]=2)[CH:8]=1)([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31]

Participants

9

Reactant 5

HCID 795ImidazoleHCID 14798Sodium HydroxideHCID 28928tert-Butyldimethylsilyl chloride2×HCID 21226445Aluminium lithium hydrideHCID 59200396HCID 59200396, compound

Product 1

HCID 59200399HCID 59200399, compoundYield 61%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolvent2×HCID 8028TetrahydrofuranSolventHCID 21908982Water methylene chlorideSolvent

Conditions

Temperature
23 °C

Procedure

A stirred suspension of methyl 2-(thiazol-2-ylamino)isonicotinate (14.17 g, 60.23 mmol) in tetrahydrofuran (385 mL) was treated with lithium aluminum hydride (2.51 g, 66.25 mmol) at 23° C. The reaction was stirred at 23° C. for 1 hour then sodium hydroxide (5N, 20 mL) was added to the mixture which was stirred again for 2 more hours. The solid was filtered and washed with tetrahydrofuran and water. The combined washings and filtrate were concentrated to give the crude alcohol (11.17 g). The crude alcohol was dissolved in N,N-dimethylformamide (150 mL) and the resulting solution was treated with imidazole (6.60 g, 97.01 mmol) and tert-butyldimethylsilyl chloride (12.19 g, 80.84 mmol) at 23° C. The reaction was stirred for 1 hour, tert-butyldimethylsilyl chloride (6.0 g) was added again and the reaction stirred for 30 more minutes. N,N-Dimethylformamide was added and the residue was taken into dichloromethane/water/saturated ammonium chloride. The organic phase was separated and the aqueous phase was extracted with dichloromethane (3×). The combined organic layers were dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by silica gel chromatography (Biotage, 0% to 70% ethyl acetate in hexanes) to give the title material (10.55 g, 61% two steps). 1H NMR (400 MHz, CDCl3) δ (ppm): 0.15 (6H, s), 0.98 (9H, s), 4.76 (2H, s), 6.81 (1H, br d, J=5.05 Hz), 6.84 (1H, d, J=3.54 Hz), 6.95 (1H, s), 7.48 (1H, d, J=3.54 Hz), 8.30 (1H, br d, J=5.31 Hz), 9.79 (1H, s). LC/MS (M+H)+: 322. HPLC ret. time (Condition A): 1.800 min.

Workup

  1. stirringwas stirred again for 2 more hours
  2. filtrationThe solid was filtered
  3. washwashed with tetrahydrofuran and water
  4. concentrationThe combined washings and filtrate were concentrated
  5. customto give the crude alcohol (11.17 g)
  6. stirringThe reaction was stirred for 1 hour
  7. stirringthe reaction stirred for 30 more minutes
  8. customThe organic phase was separated
  9. extractionthe aqueous phase was extracted with dichloromethane (3×)
  10. dry with materialThe combined organic layers were dried over anhydrous magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe residue was purified by silica gel chromatography (Biotage, 0% to 70% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-3f2f62ff5c464ea1a7efdc0b9b5e0074
Source dataset
uspto-grants-2012_04
Patent number
US08148400B2

Reaction notes

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