Ammonium Chloride → 2,5-dichloro-3-{[5-chloro-1-({1-(4-methoxybenzyl)-6-[(4-methoxybenzyl)amino]-1H-pyrazolo[3,4-b]pyridin-3-yl}methyl)-1H-1,2,3-benzotriazol-4-yl]oxy}benzonitrile

HRID 505556Notes

Reaction equation

HRID 505556 reaction equation
[Cl:1][C:2]1[C:9]([O:10][C:11]2[C:19]3[N:18]=[N:17][NH:16][C:15]=3[CH:14]=[CH:13][C:12]=2[Cl:20])=[CH:8][C:7]([Cl:21])=[CH:6][C:3]=1[C:4]#[N:5].CC(C)([O-])C.[Li+].Cl[CH2:29][C:30]1[C:38]2[C:33](=[N:34][C:35]([NH:39][CH2:40][C:41]3[CH:46]=[CH:45][C:44]([O:47][CH3:48])=[CH:43][CH:42]=3)=[CH:36][CH:37]=2)[N:32]([CH2:49][C:50]2[CH:55]=[CH:54][C:53]([O:56][CH3:57])=[CH:52][CH:51]=2)[N:31]=1.[Cl-].[NH4+]>CN(C=O)C>[Cl:1][C:2]1[C:9]([O:10][C:11]2[C:19]3[N:18]=[N:17][N:16]([CH2:29][C:30]4[C:38]5[C:33](=[N:34][C:35]([NH:39][CH2:40][C:41]6[CH:42]=[CH:43][C:44]([O:47][CH3:48])=[CH:45][CH:46]=6)=[CH:36][CH:37]=5)[N:32]([CH2:49][C:50]5[CH:51]=[CH:52][C:53]([O:56][CH3:57])=[CH:54][CH:55]=5)[N:31]=4)[C:15]=3[CH:14]=[CH:13][C:12]=2[Cl:20])=[CH:8][C:7]([Cl:21])=[CH:6][C:3]=1[C:4]#[N:5]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 236647642-Propanol, 2-methyl-, lithium salt (1:1)HCID 568336463-(Chloromethyl)-N,1-bis(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-6-amineHCID 178509931HCID 178509931, compound

Product 1

HCID 684280332,5-dichloro-3-{[5-chloro-1-({1-(4-methoxybenzyl)-6-[(4-methoxybenzyl)amino]-1H-pyrazolo[3,4-b]pyridin-3-yl}methyl)-1H-1,2,3-benzotriazol-4-yl]oxy}benzonitrile

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

2,5-dichloro-3-[(5-chloro-1H-1,2,3-benzotriazol-4-yl)oxy]benzonitrile (90 mg, 0.265 mmol) and lithium tert-butoxide (22 mg, 0.278 mmol) were dissolved in DMF (1 mL) and the solution stirred for 5 minutes at room temperature. The reaction mixture was cooled to 0° C. and 3-(chloromethyl)-N,1-bis(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-6-amine (112 mg, 0.265 mmol) in DMF (1.5 mL) was added. After the addition, the solution was allowed to warm to room temperature and stirred for 16 hours, after which saturated aqueous ammonium chloride (1 mL) was added and the mixture was extracted with ethyl acetate (2×15 mL). The combined organic fractions were washed with water (3×15 mL). The combined aqueous layers were back-extracted with EtOAc (25 mL) and the extracts subsequently washed with water (3×15 mL). The combined organic fractions were dried (MgSO4), filtered and the solvent was evaporated under reduced pressure. The resulting residue was purified by column chromatography on silica gel (12 g) eluting with 0-40% EtOAc/hexanes to afford the title compound. LRMS (M+1)=726.3.

Workup

  1. temperatureThe reaction mixture was cooled to 0° C.
  2. additionAfter the addition
  3. temperatureto warm to room temperature
  4. stirringstirred for 16 hours
  5. extractionthe mixture was extracted with ethyl acetate (2×15 mL)
  6. washThe combined organic fractions were washed with water (3×15 mL)
  7. extractionThe combined aqueous layers were back-extracted with EtOAc (25 mL)
  8. washthe extracts subsequently washed with water (3×15 mL)
  9. dry with materialThe combined organic fractions were dried (MgSO4)
  10. filtrationfiltered
  11. customthe solvent was evaporated under reduced pressure
  12. customThe resulting residue was purified by column chromatography on silica gel (12 g)
  13. washeluting with 0-40% EtOAc/hexanes

Sources & evidence

ORD record
ord-d49d905b1c15406798a5b92e8435597f
Source dataset
uspto-grants-2010_08
Patent number
US07781454B2

Reaction notes

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