Diethyl Ether → N-[1-{[3-(Aminomethyl)phenyl]methyl}-4-(methyloxy)-1H-indazol-3-yl]-5-chloro-2-thiophenesulfonamide hydrochloride

HRID 1808549Notes

Reaction equation

HRID 1808549 reaction equation
[Cl:1][C:2]1[S:6][C:5]([S:7]([NH:10][C:11]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][C:18]=3[O:20][CH3:21])[N:13]([CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([C:29]#[N:30])[CH:24]=3)[N:12]=2)(=[O:9])=[O:8])=[CH:4][CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].CCOCC>C1COCC1>[ClH:1].[NH2:30][CH2:29][C:25]1[CH:24]=[C:23]([CH2:22][N:13]2[C:14]3[C:19](=[C:18]([O:20][CH3:21])[CH:17]=[CH:16][CH:15]=3)[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:28]=[CH:27][CH:26]=1

Participants

5

Reactant 3

HCID 3283Diethyl EtherHCID 21226445Aluminium lithium hydrideHCID 59455997HCID 59455997, compound

Product 1

HCID 66632476N-[1-{[3-(Aminomethyl)phenyl]methyl}-4-(methyloxy)-1H-indazol-3-yl]-5-chloro-2-thiophenesulfonamide hydrochlorideYield 77%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a cooled, 0° C., solution of 5-chloro-N-[1-[(3-cyanophenyl)methyl]-4-(methyloxy)-1H-indazol-3-yl]-2-thiophenesulfonamide (for a preparation see Intermediate 3) (11.1 g, 24.2 mmol) in THF (150 mL) was added, dropwise maintaining temp below 10° C., 1.0M lithium aluminium hydride solution in ether (60.5 mL, 60.5 mmol), effervescence occurred, and the suspension was stirred at room temperature for one hour. The reaction was quenched by addition of water (7 mL), followed by a 2.0M solution of sodium hydroxide (42.5 mL). After stirring for 30 minutes the solid was removed by filtration and washed with THF. The combined filtrate and washings were treated with 140 g SCX silica. This was filtered and washed with methanol (1 L), and then 10% 2N hydrochloric acid in methanol (2 L). The required fractions were combined and concentrated. The resultant solid was collected by filtration and washed with water. The solid was dried in vacuo to give the title compound (N7916-76-1) (9.3 g, 77%) as a white solid. LCMS (System A) RT=0.85 min, ES+ve m/z 463/465 (M+H)+.

Workup

  1. additionwas added
  2. temperaturedropwise maintaining temp below 10° C.
  3. customThe reaction was quenched by addition of water (7 mL)
  4. stirringAfter stirring for 30 minutes the solid
  5. customwas removed by filtration
  6. washwashed with THF
  7. additionThe combined filtrate and washings were treated with 140 g SCX silica
  8. filtrationThis was filtered
  9. washwashed with methanol (1 L)
  10. concentrationconcentrated
  11. filtrationThe resultant solid was collected by filtration
  12. washwashed with water
  13. customThe solid was dried in vacuo

Sources & evidence

ORD record
ord-449cfd0dcbe246d68b5b5d145d4449e7
Source dataset
uspto-grants-2013_01
Patent number
US08357716B2

Reaction notes

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