Acetic Acid → 1-[1-(1-methyl-4-piperidinyl)-4-piperidinyl](4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine

HRID 432133Notes

Reaction equation

HRID 432133 reaction equation
[O:1]([C:8]1[CH:13]=[CH:12][C:11]([C:14]2[C:22]3[C:17](=[N:18][CH:19]=[N:20][C:21]=3[NH2:23])[N:16]([CH:24]3[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]3)[N:15]=2)=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:30][N:31]1[CH2:36][CH2:35][C:34](=O)[CH2:33][CH2:32]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C.C(=O)(O)[O-].[Na+]>O.ClCCCl>[CH3:30][N:31]1[CH2:36][CH2:35][CH:34]([N:27]2[CH2:28][CH2:29][CH:24]([N:16]3[C:17]4=[N:18][CH:19]=[N:20][C:21]([NH2:23])=[C:22]4[C:14]([C:11]4[CH:10]=[CH:9][C:8]([O:1][C:2]5[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=5)=[CH:13][CH:12]=4)=[N:15]3)[CH2:25][CH2:26]2)[CH2:33][CH2:32]1

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 740491-Methyl-4-piperidoneHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 223472623-(4-phenoxyphenyl)-1-(piperidin-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine2×

Product 1

HCID 223470911-[1-(1-methyl-4-piperidinyl)-4-piperidinyl](4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amineYield 36.9%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 962WaterSolvent

Procedure

3-(4-phenoxyphenyl)-1-(4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (Compound 2) (199 mg, 0.515 mmol), 1-methyl-4-piperidone(70 ul, 0.566 mmol), sodium triacetoxyborohydride (163 mg, 0.772 mmol) and glacial acetic acid(34 mg, 0.566 mmol) were mixed with 3 ml of 1,2-dichloroethane. After stirring at room temperature overnight, 2 ml of water was added followed by solid sodium bicarbonate until the pH reached about 8. The layers were separated and the aqueous layer was extracted with dichloromethane. The combined organic layer was washed, dried and evaporated. The residue was purified via flash column chromatography to give 92 mg of 1-[1-(1-methyl-4-piperidinyl)-4-piperidinyl](4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine. 1H NMR (DMSO) 1.47 (m, 2H), 1.72 (d, J=1 1.75 Hz, 2H), 1.88 (m, 4H), 2.14 (s, 3H), 2.35 (m, 5H), 2.81(d, J=11.32 Hz, 2H), 3.01(d, J=11.26 Hz, 2H), 4.62 (m, 1H), 7.16 (m, 5H), 7.44 (m, 2H), 7.67 (d, J=8.69 Hz, 2H), 8.23 (s, 1H); LC/MS (MH+32 484).

Workup

  1. customThe layers were separated
  2. extractionthe aqueous layer was extracted with dichloromethane
  3. washThe combined organic layer was washed
  4. customdried
  5. customevaporated
  6. customThe residue was purified via flash column chromatography

Sources & evidence

ORD record
ord-cb18a25fe37b4d46b33523ad4b7a4af9
Source dataset
uspto-grants-2003_12
Patent number
US06660744B1

Reaction notes

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