1-Methylpiperazine → 1-methyl-8-{3-[(4-methylpiperazin-1-yl)methyl]phenoxy}-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide

HRID 45793Notes

Reaction equation

HRID 45793 reaction equation
[CH:1]([C:3]1[CH:4]=[C:5]([CH:24]=[CH:25][CH:26]=1)[O:6][C:7]1[N:16]=[CH:15][C:14]2[CH:13]=[CH:12][C:11]3[C:17]([C:21]([NH2:23])=[O:22])=[N:18][N:19]([CH3:20])[C:10]=3[C:9]=2[N:8]=1)=O.[CH3:27][N:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1.C([BH3-])#N.[Na+]>CN(C)C=O.C(O)(=O)C.C(OCC)(=O)C>[CH3:20][N:19]1[C:10]2[C:9]3[N:8]=[C:7]([O:6][C:5]4[CH:24]=[CH:25][CH:26]=[C:3]([CH2:1][N:31]5[CH2:32][CH2:33][N:28]([CH3:27])[CH2:29][CH2:30]5)[CH:4]=4)[N:16]=[CH:15][C:14]=3[CH:13]=[CH:12][C:11]=2[C:17]([C:21]([NH2:23])=[O:22])=[N:18]1

Participants

7

Reactant 3

HCID 531671-MethylpiperazineHCID 5003444Sodium cyanoborohydrideHCID 57390043HCID 57390043, compound

Product 1

HCID 573900441-methyl-8-{3-[(4-methylpiperazin-1-yl)methyl]phenoxy}-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 8-(3-formylphenoxy)-1-methyl-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide 30 mg (0.086 mmol) in N,N-dimethylformamide (2 ml) and acetic acid (50 μl), N-methyl piperazine (13 μl, 0.13 mmol), and sodium cyanoborohydride (6 mg, 0.26 mmol) were added. The solution was stirred at r.t. for 3 hours, monitored by both TLC and LC/MS (method 1). The reaction was diluted with ethyl acetate, washed with water and brine, dried over Na2SO4 filtered and concentrated. The residue was purified by column (DCM/MeOH/NH4OH 95/5/0.1) to give 1-methyl-8-{3-[(4-methylpiperazin-1-yl)methyl]phenoxy}-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide as major (15 mg 40%) LC/MS (254 nm) HPLC method 2 Rt 4.14 min. 1H NMR (401 MHz, DMSO-d6) δ 9.60 (s, 1H), 8.23 (d, J=8.79 Hz, 1H), 7.83 (s, 1H), 7.78 (d, J=8.79 Hz, 1H), 7.49-7.50 (m, 1H), 7.46 (t, J=7.81 Hz, 1H), 7.26 (dt, J=1.71, 7.69 Hz, 3H), 4.27 (s, 3H), 3.53 (s, 2H), 2.30-2.47 (m, 8H), 2.17 (br. s., 3H). HRMS (ESI) calcd for C23H25N7O2 [M+H]+ 432.2143 found 432.2141; and

Workup

  1. washwashed with water and brine
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by column (DCM/MeOH/NH4OH 95/5/0.1)

Sources & evidence

ORD record
ord-e0e2ede86bf7448e85b0d3f76a454610
Source dataset
uspto-grants-2013_09
Patent number
US08541576B2

Reaction notes

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