3-(4-Methylpiperazin-1-yl)aniline → HCID 59833910, compound

HRID 270716Notes

Reaction equation

HRID 270716 reaction equation
Cl[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([C:14]3[CH:15]=[C:16]([NH:21][C:22](=[O:33])[C:23]4[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:32])([F:31])[F:30])[CH:24]=4)[CH:17]=[CH:18][C:19]=3[CH3:20])[C:8](=[O:13])[N:9]2[CH3:12])=[CH:4][N:3]=1.[CH3:34][N:35]1[CH2:40][CH2:39][N:38]([C:41]2[CH:42]=[C:43]([NH2:47])[CH:44]=[CH:45][CH:46]=2)[CH2:37][CH2:36]1.[Cl-].C(C1C=CC=C(CCC)C=1[N+]1C=CN(C2C(CCC)=CC=CC=2CCC)C=1)CC>O1CCOCC1>[CH3:20][C:19]1[CH:18]=[CH:17][C:16]([NH:21][C:22](=[O:33])[C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:30])([F:31])[F:32])[CH:24]=2)=[CH:15][C:14]=1[C:7]1[C:8](=[O:13])[N:9]([CH3:12])[C:10]2[C:5]([CH:6]=1)=[CH:4][N:3]=[C:2]([NH:47][C:43]1[CH:44]=[CH:45][CH:46]=[C:41]([N:38]3[CH2:37][CH2:36][N:35]([CH3:34])[CH2:40][CH2:39]3)[CH:42]=1)[CH:11]=2

Participants

5

Reactant 3

HCID 115646133-(4-Methylpiperazin-1-yl)anilineHCID 223147471,3-Bis(2,6-di-1-propylphenyl)imidazolium chlorideHCID 59833848Benzamide,n-[3-(7-chloro-1,2-dihydro-1-methyl-2-oxo-1,6-naphthyridin-3-yl)-4-methylphenyl]-3-(trifluoromethyl)-

Product 1

HCID 59833910HCID 59833910, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

N-[3-(7-Chloro-1-methyl-2-oxo-1,2-dihydro-[1,6]naphthyridin-3-yl)-4-methyl-phenyl]-3-trifluoromethyl-benzamide (50 mg, 0.106 mmol) is mixed with 3-(4-Methyl-piperazin-1-yl)-phenylamine (31 mg, 0.16 mmol), Pd2(dba)2 (2.4 mg, 2.5%), 1,3-Bis(2,6-di-1-propylphenyl)imidazolium chloride (2.3 mg, 5%) and potassium tert-butanoxide (17.8 mg, 0.159 mmol) under an argon environment. 6 mL of anhydrous 1,4-dioxane is added and the reaction is continued at 100° C. for 14 hours. After cooling and removal of solvent under vacuum, the crude product is dissolved in DMSO and purified by reverse phase preparative HPLC to give the final product as a pale solid: 1H NMR 400 MHz (DMSO-d6) δ 10.47 (s, 1H), 9.43 (s, 1H), 8.58 (s, 1H), 8.30 (s, 1H), 8.26 (d, 1H, J=8.1 Hz), 7.21 (d, 1H, J=7.9 Hz), 7.83 (s, 1H), 7.79 (t, 1H, J=7.8 Hz), 7.69 (m, 2H), 7.37 (s, 1H), 7.21 (m, 3H), 6.74 (s, 1H), 6.65 (d, 1H, J=6.5 Hz), 3.80 (d, 2H, J=13.9 Hz), 3.56 (s, 3H), 3.54 (d, 2H, J=13.9 Hz), 3.18 (m, 2H), 2.98 (m, 2H), 2.88 (d, 3H, J=3.8 Hz), 2.14 (s, 3H); MS m/z 627.3 (M+1).

Workup

  1. temperatureAfter cooling
  2. customremoval of solvent under vacuum
  3. dissolutionthe crude product is dissolved in DMSO
  4. custompurified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-69a181628f774e6aa7432db790e69d8e
Source dataset
uspto-grants-2008_11
Patent number
US07449582B2

Reaction notes

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