Aluminium lithium hydride → HCID 66741956, compound

HRID 337316Notes

Reaction equation

HRID 337316 reaction equation
C([O:3][C:4](=O)[C:5]([O:8][C:9]1[CH:10]=[N:11][C:12]([NH:15][C:16]2[C:17](=[O:24])[N:18]([CH3:23])[N:19]=[C:20]([Cl:22])[CH:21]=2)=[CH:13][CH:14]=1)([CH3:7])[CH3:6])C.C(=O)=O.C(#N)C.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1>[Cl:22][C:20]1[CH:21]=[C:16]([NH:15][C:12]2[CH:13]=[CH:14][C:9]([O:8][C:5]([CH3:7])([CH3:6])[CH2:4][OH:3])=[CH:10][N:11]=2)[C:17](=[O:24])[N:18]([CH3:23])[N:19]=1

Participants

5

Reactant 3

HCID 21226445Aluminium lithium hydrideHCID 66742549HCID 66742549, compoundHCID 86587134Acetonitrile dry ice

Product 1

HCID 66741956HCID 66741956, compoundYield 95.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-20 °C

Procedure

2-[6-(6-Chloro-2-methyl-3-oxo-2,3-dihydro-pyridazin-4-ylamino)-pyridin-3-yloxy]-2-methyl-propionic acid ethyl ester (1.23 g, 3.35 mmol, Eq: 1.00) was dissolved in anhydrous THF (25 ml) and cooled to −30° C. (dry ice/acetonitrile cooling bath) under nitrogen atmosphere A solution of lithium aluminum hydride (4.7 ml, 4.69 mmol, 1.0 M in THF) was added slowly, over 10 minutes via drop-wise addition. The mixture was stirred for 1 hour while maintaining the bath temperature at about −20° C. The reaction was carefully quenched by adding water (0.1 ml) and stirring for 10 minutes at ambient. Then a 5% aqueous solution of sodium hydroxide (0.19 ml) was added and the mixture stirred for 10 minutes. Water (0.19 ml) was added and stirring continued for 10 minutes. Finally magnesium sulfate was added and the material was filtered through a plug of celite, rinsing well with tetrahydrofuran. The combined filtrate and washes were concentrated on a rotary evaporator to about half the volume. Ethyl acetate (50 ml) and water (70 ml) was added and the material was shaken in a separatory funnel. The organic phase was collected and the aqueous phase was back extracted with ethyl acetate (2×40 ml). The organics were combined, dried with magnesium sulfate, filtered and concentrated in vacuo. The residue was triturated from hot dichloromethane/hexanes to provide the desired product as a light yellow-brown solid (1.041 g). (M+H)=325 m/e. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.28 (s, 6 H) 3.81 (s, 3 H) 6.92 (d, J=8.69 Hz, 1 H) 7.30 (s, 1 H) 7.36 (dd, J=8.69, 2.64 Hz, 1 H) 8.12 (d, J=2.64 Hz, 1 H) 8.28 (s, 1 H).

Workup

  1. additionwas added slowly, over 10 minutes via drop-wise addition
  2. customThe reaction was carefully quenched
  3. additionby adding water (0.1 ml)
  4. stirringstirring for 10 minutes at ambient
  5. additionThen a 5% aqueous solution of sodium hydroxide (0.19 ml) was added
  6. stirringthe mixture stirred for 10 minutes
  7. additionWater (0.19 ml) was added
  8. stirringstirring
  9. waitcontinued for 10 minutes
  10. additionFinally magnesium sulfate was added
  11. filtrationthe material was filtered through a plug of celite
  12. washrinsing well with tetrahydrofuran
  13. concentrationThe combined filtrate and washes were concentrated on a rotary evaporator to about half the volume
  14. additionEthyl acetate (50 ml) and water (70 ml) was added
  15. stirringthe material was shaken in a separatory funnel
  16. customThe organic phase was collected
  17. extractionthe aqueous phase was back extracted with ethyl acetate (2×40 ml)
  18. dry with materialdried with magnesium sulfate
  19. filtrationfiltered
  20. concentrationconcentrated in vacuo
  21. customThe residue was triturated from hot dichloromethane/hexanes

Sources & evidence

ORD record
ord-d2a6d089cfda4aaaa3591bd10004911c
Source dataset
uspto-grants-2014_11
Patent number
US08889682B2

Reaction notes

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