Sodium Hydroxide → HCID 20817140, compound

HRID 897730Notes

Reaction equation

HRID 897730 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[N:14][C:15]=3[NH2:17])[N:10]([CH:18]3[CH2:23][CH2:22][N:21]([CH:24]4[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]4)[CH2:20][CH2:19]3)[N:9]=2)=[CH:4][C:3]=1[O:31][CH3:32].[C:33]1([C@H:39]([CH3:44])[CH2:40][C:41](Cl)=[O:42])[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.[OH-].[Na+]>N1C=CC=CC=1.ClCCl>[OH-:31].[NH4+:1].[NH2:17][C:15]1[N:14]=[CH:13][N:12]=[C:11]2[N:10]([CH:18]3[CH2:23][CH2:22][N:21]([CH:24]4[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]4)[CH2:20][CH2:19]3)[N:9]=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([NH:1][C:41](=[O:42])[CH2:40][C@H:39]([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)[CH3:44])=[C:3]([O:31][CH3:32])[CH:4]=3)[C:16]=12

Participants

7

Reactant 3

HCID 14798Sodium HydroxideHCID 7021725HCID 7021725, compound2×HCID 223469753-(4-amino-3-methoxyphenyl)-1-[1-(1-methylpiperidin-4-yl)piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine

Product 2

HCID 14923Ammonium HydroxideYield 2%HCID 20817140HCID 20817140, compoundYield 112.8%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
-5 °C

Procedure

A solution of 3-(4-amino-3-methoxyphenyl)-1-[1-(1-methylpiperidin-4-yl)piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.500 g, 1.15 mmol) in pyridine (8 mL) at −5° C. was treated with a solution of (3R)-3-phenylbutanoyl chloride (0.420 g, 2.3 mmol) in dichloromethane (3 mL). The reaction mixture stirred for 20 min at −5° C., then the dry ice/acetone bath was removed and was stirred at room temperature under a nitrogen atmosphere. (3R)-3-phenylbutanoyl chloride (0.210 g, 1.15 mmol) was added to the reaction mixture and was stirred for 2 h. Sodium hydroxide (1 N) solution (10 mL) was added and was stirred over night. The organic solvent was removed under reduced pressure, and dichloromethane (20 mL) was added. The layers were partitioned, and the aqueous layer was extracted with dichloromethane (125 mL). The combined organic layers were washed with water, dried over magnesium sulfate, filtered and the solvent removed under reduced pressure. N1-(4-{4-amino-1-[1-(1-methylpiperidin-4-yl)piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-(3R)-3-phenylbutanamide was purified by flash chromatography on silica gel using 15% (methanol with 2% ammonium hydroxide) in dichloromethane (10 min), 20% (methanol with 2% ammonium hydroxide) in dichloromethane (15 min), 50% (methanol with 2% ammonium hydroxide) in dichloromethane (7 min) to give 0.378 g (57%) pure N1-(4-{4-amino-1-[1-(1-methylpiperidin-4-yl)piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-(3R)-3-phenylbutanamide. A warmed solution of N1-(4-{4-amino-1-[1-(1-methylpiperidin-4-yl)piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-(3R)-3-phenylbutanamide (0.378 g, 0.649 mmol) in ethyl acetate was treated with a warmed solution of maleic acid (0.226 g, 1.95 mmol) in ethyl acetate. The precipitate was filtered under nitrogen and dried on lyophilizer to give N1-(4-{4-amino-1-[1-(1-methylpiperidin-4-yl)piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-(3R)-3-phenylbutanamide trimaleate.

Workup

  1. customthe dry ice/acetone bath was removed
  2. stirringwas stirred at room temperature under a nitrogen atmosphere
  3. stirringwas stirred for 2 h
  4. stirringwas stirred over night
  5. customThe organic solvent was removed under reduced pressure, and dichloromethane (20 mL)
  6. additionwas added
  7. customThe layers were partitioned
  8. extractionthe aqueous layer was extracted with dichloromethane (125 mL)
  9. washThe combined organic layers were washed with water
  10. dry with materialdried over magnesium sulfate
  11. filtrationfiltered
  12. customthe solvent removed under reduced pressure
  13. customN1-(4-{4-amino-1-[1-(1-methylpiperidin-4-yl)piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-(3R)-3-phenylbutanamide was purified by flash chromatography on silica gel using 15% (methanol with 2% ammonium hydroxide) in dichloromethane (10 min), 20% (methanol with 2% ammonium hydroxide) in dichloromethane (15 min)

Sources & evidence

ORD record
ord-ee6e8524f9954145b1555ab4a4636859
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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