1-Methylpiperazine → N-{4-[(4-methylpiperazin-1-yl)carbonyl]phenyl}-4-(1-phenyl-1H-pyrazol-5-yl) pyrimidin-2-amine

HRID 2214781Notes

Reaction equation

HRID 2214781 reaction equation
[C:1]1([N:7]2[C:11]([C:12]3[CH:17]=[CH:16][N:15]=[C:14]([NH:18][C:19]4[CH:27]=[CH:26][CH:25]=[CH:24][C:20]=4C(O)=O)[N:13]=3)=[CH:10][CH:9]=[N:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:28][N:29]1[CH2:34]CNCC1.Cl.[CH3:36][N:37]([CH3:46])[CH2:38][CH2:39]CN=C=NCC.[OH:47]N1C2N=CC=CC=2N=N1>CN(C=O)C>[CH3:28][N:29]1[CH2:39][CH2:38][N:37]([C:36]([C:25]2[CH:26]=[CH:27][C:19]([NH:18][C:14]3[N:13]=[C:12]([C:11]4[N:7]([C:1]5[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=5)[N:8]=[CH:9][CH:10]=4)[CH:17]=[CH:16][N:15]=3)=[CH:20][CH:24]=2)=[O:47])[CH2:46][CH2:34]1

Participants

6

Reactant 4

HCID 531671-MethylpiperazineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86595126[4-(1-phenyl-1H-pyrazol-5-yl]pyrimidin-2-yl}amino benzoic acid

Product 1

HCID 10225209N-{4-[(4-methylpiperazin-1-yl)carbonyl]phenyl}-4-(1-phenyl-1H-pyrazol-5-yl) pyrimidin-2-amine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
23 °C

Procedure

A mixture of 4-{[4-(1-phenyl-1H-pyrazol-5-yl)pyrimidin-2-yl]amino}benzoic acid (2-2, 60 mg, 0.16 mmol, 1 equiv), 1-methylpiperazine (49 mg, 0.49 mmol, 3.0 equiv), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (47 mg, 0.24 mmol, 1.5 equiv), 1-hydroxy-7-azabenzotriazole (37 mg, 0.24 mmol, 1.5 equiv) in DMF (40 mL) was stirred for 20 hours at 23° C. The reaction mixture was partitioned between water (75 mL) and ethyl acetate (2×50 mL). The combined organic layers were dried over sodium sulfate and concentrated. The residue was purified by reverse-phase LC (H2O/CH3CN gradient w/0.1% TFA present) to provide N-{4-[(4-methylpiperazin-1-yl)carbonyl]phenyl}-4-(1-phenyl-1H-pyrazol-5-yl)pyrimidin-2-amine (2-3) as an off-white solid. 1H NMR (300 MHz, DMSO-d6, TFA salt) δ 9.93 (s, 1H), 9.87 (br s, 1H), 8.59 (d, 1H, J=4.9 Hz), 7.86 (d, 1H, J=1.8 Hz), 7.51–7.33 (m, 5H), 7.23 (d, 2H, J=8.2 Hz), 7.17 (d, 2H, J=8.6 Hz), 7.06 (m, 2H), 4.20 (br m, 2H), 3.49 (br m, 2H), 3.28 (br m, 2H), 3.10 (br m, 2H), 2.85 (s, 3H).

Workup

  1. customThe reaction mixture was partitioned between water (75 mL) and ethyl acetate (2×50 mL)
  2. dry with materialThe combined organic layers were dried over sodium sulfate
  3. concentrationconcentrated
  4. customThe residue was purified by reverse-phase LC (H2O/CH3CN gradient w/0.1% TFA present)

Sources & evidence

ORD record
ord-f4ab1ee02c7046359422af0cd15c7800
Source dataset
uspto-grants-2006_09
Patent number
US07109204B2

Reaction notes

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