2-Propanol, 2-methyl-, lithium salt (1:1) → 3-chloro-5-{[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 505527Notes

Reaction equation

HRID 505527 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([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:9]=1)[C:5]#[N:6].CC(C)([O-])C.[Li+].Cl[CH2:28][C:29]1[C:37]2[C:32](=[N:33][C:34]([NH:38][CH2:39][C:40]3[CH:45]=[CH:44][C:43]([O:46][CH3:47])=[CH:42][CH:41]=3)=[CH:35][CH:36]=2)[N:31]([CH2:48][C:49]2[CH:54]=[CH:53][C:52]([O:55][CH3:56])=[CH:51][CH:50]=2)[N:30]=1>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([O:10][C:11]2[C:19]3[N:18]=[N:17][N:16]([CH2:28][C:29]4[C:37]5[C:32](=[N:33][C:34]([NH:38][CH2:39][C:40]6[CH:41]=[CH:42][C:43]([O:46][CH3:47])=[CH:44][CH:45]=6)=[CH:35][CH:36]=5)[N:31]([CH2:48][C:49]5[CH:50]=[CH:51][C:52]([O:55][CH3:56])=[CH:53][CH:54]=5)[N:30]=4)[C:15]=3[CH:14]=[CH:13][C:12]=2[Cl:20])[CH:9]=1)[C:5]#[N:6]

Participants

5

Reactant 3

HCID 236647642-Propanol, 2-methyl-, lithium salt (1:1)HCID 568336463-(Chloromethyl)-N,1-bis(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-6-amineHCID 178509930HCID 178509930, compound

Product 1

HCID 684256713-chloro-5-{[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×

Conditions

Temperature
0 °C

Procedure

3-chloro-5-[(5-chloro-1H-1,2,3-benzotriazol-4-yl)oxy]benzonitrile (140 mg, 0.459 mmol) and lithium tert-butoxide (37 mg, 0.459 mmol) were dissolved in DMF (1 mL) under N2 and allowed to stir for 20 minutes. After this time, the reaction was cooled to 0° C. and 3-(chloromethyl)-N,1-bis(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-6-amine as a solution in DMF (1 mL) was added dropwise. After 1 hour, the reaction was quenched with saturated aqueous ammonium chloride (3 mL), diluted with water (3 mL) and the mixture was extracted with ethyl acetate (2×25 mL). The combined organic fractions were washed with dilute brine (4×10 mL), dried (MgSO4), filtered and the solvent was evaporated under reduced pressure. The resulting residue was purified by automated column chromatography on silica gel (12 g), eluting with 0-100% EtOAc/hexanes to give the title compound. LRMS (M+1)=690.5.

Workup

  1. waitAfter 1 hour
  2. customthe reaction was quenched with saturated aqueous ammonium chloride (3 mL)
  3. additiondiluted with water (3 mL)
  4. extractionthe mixture was extracted with ethyl acetate (2×25 mL)
  5. washThe combined organic fractions were washed with dilute brine (4×10 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customthe solvent was evaporated under reduced pressure
  9. customThe resulting residue was purified by automated column chromatography on silica gel (12 g)
  10. washeluting with 0-100% EtOAc/hexanes

Sources & evidence

ORD record
ord-e17ae3e32d1f453b9129fd5df53d89d2
Source dataset
uspto-grants-2010_08
Patent number
US07781454B2

Reaction notes

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