Hydrochloric Acid → 4-(5-(3-(9-(4-methoxybenzyl)-9H-purin-6-yl)pyridin-2-ylamino)-6-methylisoquinolin-1-ylamino)benzonitrile

HRID 1042273Notes

Reaction equation

HRID 1042273 reaction equation
[NH2:1][C:2]1[C:11]([CH3:12])=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[C:7]2[NH:13][C:14]1[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][CH:15]=1.[CH3:22][O:23][C:24]1[CH:46]=[CH:45][C:27]([CH2:28][N:29]2[CH:37]=[N:36][C:35]3[C:30]2=[N:31][CH:32]=[N:33][C:34]=3[C:38]2[C:39](F)=[N:40][CH:41]=[CH:42][CH:43]=2)=[CH:26][CH:25]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].Cl.C([O-])(O)=O.[Na+]>C1COCC1>[CH3:22][O:23][C:24]1[CH:25]=[CH:26][C:27]([CH2:28][N:29]2[CH:37]=[N:36][C:35]3[C:30]2=[N:31][CH:32]=[N:33][C:34]=3[C:38]2[C:39]([NH:1][C:2]3[C:11]([CH3:12])=[CH:10][CH:9]=[C:8]4[C:3]=3[CH:4]=[CH:5][N:6]=[C:7]4[NH:13][C:14]3[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][CH:15]=3)=[N:40][CH:41]=[CH:42][CH:43]=2)=[CH:45][CH:46]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 2733832Lithium HexamethyldisilazideHCID 59627379HCID 59627379, compoundHCID 687254604-(5-Amino-6-methylisoquinolin-1-ylamino)benzonitrile

Product 1

HCID 687244614-(5-(3-(9-(4-methoxybenzyl)-9H-purin-6-yl)pyridin-2-ylamino)-6-methylisoquinolin-1-ylamino)benzonitrile

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 4-(5-amino-6-methylisoquinolin-1-ylamino)benzonitrile (0.250 g, 0.91 mmol) and 9-(4-methoxybenzyl)-6-(2-fluoropyridin-3-yl)-9H-purine (0.34 g, 1.0 mmol) in anhydrous THF (20 mL) was treated dropwise with lithium bis(trimethylsilyl)amide (1.0 M solution in THF; 2.7 mlL, 2.7 mmol) to give a dark suspension. The suspension was sonicated for 2 min and then stirred at RT for 30 min. The reaction mixture was sonicated again for 2 min. The mixture was treated with 1N aq HCl (5 mL) and stirred at RT for 10 min. The reaction mixture was added to satd NaHCO3 (70 mL) and extracted with 3:1 CHCl3:IPA (3×50 mL). The combined organic layers were washed with satd NaCl, dried over Na2SO4, filtered, and concentrated in vacuo to give 840 mg crude product. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Redi-Sep® pre-packed silica gel column (80 g), eluting with a gradient of 10% to 50% EtOAc in CH2Cl2, to give 4-(5-(3-(9-(4-methoxybenzyl)-9H-purin-6-yl)pyridin-2-ylamino)-6-methylisoquinolin-1-ylamino)benzonitrile. MS (ESI, pos. ion) m/z: 590.2 [M+H]+

Workup

  1. customto give a dark suspension
  2. customThe suspension was sonicated for 2 min
  3. customThe reaction mixture was sonicated again for 2 min
  4. stirringstirred at RT for 10 min
  5. extractionextracted with 3:1 CHCl3
  6. washThe combined organic layers were washed with satd NaCl
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto give 840 mg crude product
  11. customchromatographed through a Redi-Sep® pre-packed silica gel column (80 g)
  12. washeluting with a gradient of 10% to 50% EtOAc in CH2Cl2

Sources & evidence

ORD record
ord-6516a53259c5435e9f881a76fbbe0139
Source dataset
uspto-grants-2013_10
Patent number
US08557830B2

Reaction notes

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