Aluminium lithium hydride → HCID 59456097, compound

HRID 1808581Notes

Reaction equation

HRID 1808581 reaction equation
[Cl:1][C:2]1[S:6][C:5]([S:7]([NH:10][C:11]2[C:19]3[C:14](=[C:15]([F:22])[CH:16]=[CH:17][C:18]=3[O:20][CH3:21])[N:13]([CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([C:30]#[N:31])[CH:25]=3)[N:12]=2)(=[O:9])=[O:8])=[CH:4][CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1.C(OCC)C>[NH2:31][CH2:30][C:26]1[CH:25]=[C:24]([CH2:23][N:13]2[C:14]3[C:19](=[C:18]([O:20][CH3:21])[CH:17]=[CH:16][C:15]=3[F:22])[C:11]([NH:10][S:7]([C:5]3[S:6][C:2]([Cl:1])=[CH:3][CH:4]=3)(=[O:9])=[O:8])=[N:12]2)[CH:29]=[CH:28][CH:27]=1

Participants

5

Reactant 2

HCID 21226445Aluminium lithium hydride2×HCID 59456027HCID 59456027, compound

Product 1

HCID 59456097HCID 59456097, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

5-Chloro-N-[1-[(3-cyanophenyl)methyl]-7-fluoro-4-(methyloxy)-1H-indazol-3-yl]-2-thiophenesulfonamide (for a preparation see Intermediate 45) (600 mg, 1.26 mmol) was dissolved in THF (13 mL) and stirred in an ice bath. The solution was then treated dropwise with lithium aluminium hydride (1M in diethyl ether) (0.881 mL, 0.881 mmol) and stirred under nitrogen overnight. Further six portions of lithium aluminium hydride (1M in diethyl ether, 0.126 mL at a time) were added dropwise to the reaction and stirred for another day. The reaction was quenched with 2M NaOH solution (4 mL) and extracted with ethyl acetate (100 mL). The organic layer was washed with brine (100 mL) before being dried over anhydrous magnesium sulphate and evaporated in vacuo. The residue was dissolved in methanol and loaded onto a methanol conditioned sulfonic acid cartridge (SCX-2) 50 g. The cartridge was washed with methanol and eluted with 2M ammonia in methanol. Ammoniacal fractions were evaporated to give a brown gum (100 mg). The aqueous layer was back extracted with ethyl acetate (100 mL). The organic layer was washed with brine (100 mL) and dried over anhydrous magnesium sulphate before being evaporated in vacuo to give a brown gum (60 mg). The aqueous layer was back extracted with chloroform-isopropanol 3:1 (100 mL). The organic layer was dried over anhydrous magnesium sulphate before being evaporated in vacuo to a further 40 mg. The solids in the aqueous layer were collected by filtration. The solid was dissolved in methanol and filtered to remove any insoluble material. The filtrate was evaporated in vacuo to a further batch of 300 mg. The combined batches were dissolved in methanol and loaded onto a methanol pre-conditioned 50 g sulfonic acid (SCX-2) cartridge. The cartridge was washed with methanol and then eluted with 2M ammonia in methanol. Ammoniacal fractions were evaporated in vacuo to give the title compound as a brown gum (220 mg) LCMS (System A) RT=0.81 min, ES+ve m/z 481/483 (M+H)+.

Workup

  1. stirringstirred under nitrogen overnight
  2. stirringstirred for another day
  3. customThe reaction was quenched with 2M NaOH solution (4 mL)
  4. extractionextracted with ethyl acetate (100 mL)
  5. washThe organic layer was washed with brine (100 mL)
  6. dry with materialbefore being dried over anhydrous magnesium sulphate
  7. customevaporated in vacuo
  8. dissolutionThe residue was dissolved in methanol
  9. washThe cartridge was washed with methanol
  10. washeluted with 2M ammonia in methanol
  11. customAmmoniacal fractions were evaporated

Sources & evidence

ORD record
ord-db9e1994a5f740edaf81dd933eb16abe
Source dataset
uspto-grants-2013_01
Patent number
US08357716B2

Reaction notes

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