Acetic Acid → HCID 178481014, compound

HRID 432161Notes

Reaction equation

HRID 432161 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]3[CH2:17][CH2:16][C:15](=O)[CH2:14][CH2:13]3)[N:9]=[C:10]([I:11])[C:3]=12.[CH3:19][N:20]1[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[I:11][C:10]1[C:3]2[C:4](=[N:5][CH:6]=[N:7][C:2]=2[NH2:1])[N:8]([C@H:12]2[CH2:17][CH2:16][C@@H:15]([N:23]3[CH2:24][CH2:25][N:20]([CH3:19])[CH2:21][CH2:22]3)[CH2:14][CH2:13]2)[N:9]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 531671-MethylpiperazineHCID 5049666Sodium triacetoxyborohydride2×HCID 223467294-(4-Amino-3-iodo-1h-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexanone

Product 1

HCID 178481014HCID 178481014, compoundYield 56.8%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
40 °C

Procedure

A mixture of 4-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-1-cyclohexanone (Intermediate AK) (1.32 g, 0.0037 mol), N-methylpiperazine (1.11 g, 0.011 mol) and acetic acid (0.66 g, 0.011 mol) in 1,2-dichloroethane (50 mL) was stirred for 10 min at 40° C. and sodium triacetoxyborohydride (1.09 g, 0.0052 mol) was added at once. The mixture was stirred at ambient temperature under an atmosphere of nitrogen for 24 hours and sodium triacetoxyborohydride (0.25 g, 0.0012 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 chloroform (50 mL). The organic layer was separated and the aqueous layer further extracted with chloroform (3×50 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 (88:11:1) as a mobile phase to yield cis-3-iodo-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine as a white solid (0.93 g, 0.0021 mol): 1H NMR (DMSO-d6, 400 MHz) 8.18 (s, 1H), 4.71 (m, 1H), 2.38-1.9 (m, 13H), 2.17 (s, 3H), 1.63-1.5 (m, 4H); TLC (dichloromethane/triethylamine=9:1) Rf 0.24 and trans-3-iodo-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine as a white solid (0.38 g, 0.00086 mol): 1H NMR (DMSO-d6, 400 MHz) 8.18 (s, 1H), 4.55 (m, 1H), 2.38-1.9 (m, 15H), 2.15 (s, 3H), 1.42 (m, 2H); TLC (dichloromethane/triethylamine=9:1) Rf 0.11.

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 chloroform (50 mL)
  5. customThe organic layer was separated
  6. extractionthe aqueous layer further extracted with chloroform (3×50 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-0ecaa28649894c07b143c4b174025404
Source dataset
uspto-grants-2003_12
Patent number
US06660744B1

Reaction notes

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