Acetic Acid → HCID 178480994, compound

HRID 897458Notes

Reaction equation

HRID 897458 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:24]3[CH2:29][CH2:28][C:27](=O)[CH2:26][CH2:25]3)[N:9]=[C:10]([C:11]3[CH:12]=[N:13][C:14]([O:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[CH:15][CH:16]=3)[C:3]=12.[CH3:31][N:32]1[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH3:31][N:32]1[CH2:37][CH2:36][N:35]([C@@H:27]2[CH2:26][CH2:25][C@H:24]([N:8]3[C:4]4=[N:5][CH:6]=[N:7][C:2]([NH2:1])=[C:3]4[C:10]([C:11]4[CH:12]=[N:13][C:14]([O:17][C:18]5[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=5)=[CH:15][CH:16]=4)=[N:9]3)[CH2:29][CH2:28]2)[CH2:34][CH2:33]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 531671-MethylpiperazineHCID 5049666Sodium triacetoxyborohydride2×HCID 223467504-[4-amino-3-(6-phenoxy-3-pyridyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-cyclo-hexanone

Product 1

HCID 178480994HCID 178480994, compound

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A mixture of 4-[4-amino-3-(6-phenoxy-3-pyridyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-cyclo-hexanone (Intermediate Al) (0.90 g, 0.0022 mol), N-methylpiperazine (0.676 g, 0.0067 mol) and acetic acid (0.405 g, 0.0067 mol) in 1,2-dichloroethane (40 mL) was stirred for 10 min and sodium triacetoxyborohydride (0.62 g, 0.0029 mol) was added at once. The mixture was stirred at ambient temperature under an atmosphere of nitrogen for 24 hours and sodium triacetoxyborohydride (0.30 g, 0.0014 mol) was added. The mixture was stirred for another 48 hours, the solvent removed under reduced pressure and the residue partitioned between saturated aqueous sodium bicarbonate solution (80 mL) and dichloromethane (50 mL). The organic layer was separated and the aqueous layer further extracted with dichloromethane twice (50 mL). The combined organic extracts were dried over magnesium sulfate and the solvent removed under reduced pressure to yield a yellow oil. The compound was further purified by flash chromatography on silica gel using dichloromethane/triethylamine/methanol (89:10:1) as a mobile phase to yield cis-1-[4-(4-methylpiperazino)cyclohexyl]-3-(6-phenoxy-3-pyridyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (Intermediate AJ): TLC (dichloromethane/triethylamine 9:1) Rf 0.29 and trans-1-[4-(4-methylpiperazino)cyclohexyl]-3-(6-phenoxy-3-pyridyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine: TLC (dichloromethane/triethylamine=9:1) Rf 0.14.

Workup

  1. stirringThe mixture was stirred at ambient temperature under an atmosphere of nitrogen for 24 hours
  2. stirringThe mixture was stirred for another 48 hours
  3. customthe solvent removed under reduced pressure
  4. customthe residue partitioned between saturated aqueous sodium bicarbonate solution (80 mL) and dichloromethane (50 mL)
  5. customThe organic layer was separated
  6. extractionthe aqueous layer further extracted with dichloromethane twice (50 mL)
  7. dry with materialThe combined organic extracts were dried over magnesium sulfate
  8. customthe solvent removed under reduced pressure
  9. customto yield a yellow oil
  10. customThe compound was further purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-705cd41d69254d6c9cabee643ac65feb
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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