Acetic Acid → 1-[4-(4-methylpiperazino)cyclohexyl]-3-{4-[(phenethylamino)(phenyl)methyl]phenyl}-1H-pyrazolo[3,4-d]pyrimidin-4-amine

HRID 432251Notes

Reaction equation

HRID 432251 reaction equation
[NH2:1][CH:2]([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:17]3[C:12](=[N:13][CH:14]=[N:15][C:16]=3[NH2:18])[N:11]([C@H:19]3[CH2:24][CH2:23][C@@H:22]([N:25]4[CH2:30][CH2:29][N:28]([CH3:31])[CH2:27][CH2:26]4)[CH2:21][CH2:20]3)[N:10]=2)=[CH:5][CH:4]=1.[C:38]1([CH2:44][CH:45]=O)[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH3:31][N:28]1[CH2:27][CH2:26][N:25]([CH:22]2[CH2:23][CH2:24][CH:19]([N:11]3[C:12]4=[N:13][CH:14]=[N:15][C:16]([NH2:18])=[C:17]4[C:9]([C:6]4[CH:5]=[CH:4][C:3]([CH:2]([NH:1][CH2:45][CH2:44][C:38]5[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=5)[C:32]5[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=5)=[CH:8][CH:7]=4)=[N:10]3)[CH2:20][CH2:21]2)[CH2:30][CH2:29]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 998PhenylacetaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 178480954HCID 178480954, compound

Product 1

HCID 223466841-[4-(4-methylpiperazino)cyclohexyl]-3-{4-[(phenethylamino)(phenyl)methyl]phenyl}-1H-pyrazolo[3,4-d]pyrimidin-4-amineYield 46.6%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of cis-3-{4-[amino(phenyl)methyl]phenyl}-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (50 mg, 0.10 mmol), phenylacetaldehyde (13 mg) and glacial acetic acid (0.013 mL) in 1,2-dichloroethane (1 mL) under nitrogen was added sodium triacetoxyborohydride (2 equivs., 43 mg). The solution was stirred for 18 h then concentrated in vacuo, partitioned between dichloromethane (10 mL) and saturated aqueous NaHCO3 (10 mL) and the organic layer separated. The aqueous layer was further extracted with dichloromethane (4×10 mL) and the combined organic layers were dried over anhydrous magnesium sulfate and evaporated to dryness. Purification was effected using mass actuated preparative RP-HPLC (Micromass/Gilson, Hypersil BDS C18, 5 μm, 100×21.2 mm column; 0-100% acetonitrile and 0.05M ammonium acetate, buffered to pH 4.5, over 12.5 min at 25 mL/min) to afford 1-[4-(4-methylpiperazino)cyclohexyl]-3-{4-[(phenethylamino)(phenyl)methyl]phenyl}-1H-pyrazolo[3,4-d]pyrimidin-4-amine (28 mg); RP-HPLC (10 to 90% CH3CN in 0.1 N aqueous ammonium acetate, buffered to pH 4.5, over 12 min at 2 mL/min using a Waters Symmetry C18, 250×4.6 mm column) Rt=12.269 min, 95.2%; m/z (MH+) 601.3.

Workup

  1. concentrationthen concentrated in vacuo
  2. custompartitioned between dichloromethane (10 mL) and saturated aqueous NaHCO3 (10 mL)
  3. customthe organic layer separated
  4. extractionThe aqueous layer was further extracted with dichloromethane (4×10 mL)
  5. dry with materialthe combined organic layers were dried over anhydrous magnesium sulfate
  6. customevaporated to dryness
  7. customPurification
  8. customRP-HPLC (Micromass/Gilson, Hypersil BDS C18, 5 μm, 100×21.2 mm column; 0-100% acetonitrile and 0.05M ammonium acetate, buffered to pH 4.5, over 12.5 min at 25 mL/min)

Sources & evidence

ORD record
ord-489b1bc85d2e4b2fa966be0e7b55003d
Source dataset
uspto-grants-2003_12
Patent number
US06660744B1

Reaction notes

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