1-Methylpiperazine → HCID 86613337, compound

HRID 2109806Notes

Reaction equation

HRID 2109806 reaction equation
COC1C=CC([C:9]2[CH:10]=[N:11][C:12]([NH:15][C:16]3[CH:17]=[C:18](NC(N4CCN(C)CC4)=O)[CH:19]=[CH:20][CH:21]=3)=[N:13][CH:14]=2)=CC=1.[CH3:32][O:33][C:34]1[CH:39]=[CH:38][C:37](C2C=NC(NC3C=CC=C(N)C=3)=NC=2)=[CH:36][CH:35]=1.C([N:57](C(C)C)CC)(C)C.ClC(Cl)(O[C:67](=[O:73])OC(Cl)(Cl)Cl)Cl.[CH3:75][N:76]1[CH2:81][CH2:80][NH:79][CH2:78][CH2:77]1>C1COCC1>[CH3:32][O:33][C:34]1[CH:35]=[CH:36][C:37]([C:19]2[CH:18]=[CH:17][C:16]([NH:15][C:12]3[N:13]=[CH:14][CH:9]=[CH:10][N:11]=3)=[C:21]([CH:81]3[N:76]([CH3:75])[CH2:77][CH2:78][N:79]([C:67]([NH2:57])=[O:73])[CH2:80]3)[CH:20]=2)=[CH:38][CH:39]=1

Participants

7

Reactant 5

HCID 531671-MethylpiperazineHCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 16129429HCID 16129429, compoundHCID 57632682HCID 57632682, compound

Product 1

HCID 86613337HCID 86613337, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

N-(3-(5-(4-methoxyphenyl)pyrimidin-2-ylamino)phenyl)-4-methylpiperazine-1-carboxamide can be prepared by the following procedure. To a solution of N1-(5-(4-methoxyphenyl)pyrimidin-2-yl)benzene-1,3-diamine (0.34 mmol) (From Example 5av) in THF (7 mL) are added diisopropylethylamine (0.75 mmol) and triphosgene (0.10 mmol). After stirring for 30 min at rt, 1-methylpiperazine (1.02 mmol) is added and stirring is continued for 1 h. The reaction is partitioned between dichloromethane and water. The organic layer is washed with brine, dried over magnesium sulfate, filtered and the solvent is removed. The crude product is crystallized from dichloromethane to afford the desired product as a white crystalline solid (50%). 1H NMR (400 MHz, DMSO-d6) δ 9.63 (s, 1H), 8.76 (s, 2H), 8.49 (s, 1H), 7.83 (t, J=2.0 Hz, 1H), 7.64 (d, J=8.4 Hz, 2H), 7.37 (d, J=7.0 Hz, 1H), 7.13 (t, J=8.0 Hz, 1H), 7.05 (d, J=7.0 Hz, 1H), 7.04 (d, J=8.0 Hz, 2H), 3.80 (s, 3H), 3.44 (bs, 4H), 2.33 (bs, 4H), 2.22 (s, 3H). MS (m/z) (M+1)+ 419.2.

Workup

  1. stirringstirring
  2. waitis continued for 1 h
  3. customThe reaction is partitioned between dichloromethane and water
  4. washThe organic layer is washed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customthe solvent is removed
  8. customThe crude product is crystallized from dichloromethane

Sources & evidence

ORD record
ord-7d21bfdb127a437eb38d65bf36e7d094
Source dataset
uspto-grants-2009_04
Patent number
US07514447B2

Reaction notes

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