Isopropanol → 6-(5-Methyl-2-(6-(4-methylpiperazin-1-yl)pyridin-3-ylamino)pyrimidin-4-ylamino)benzo[d]oxazol-2(3H)-one

HRID 39325

Reaction equation

HRID 39325 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:18]=[CH:17][C:12]3[NH:13][C:14](=[O:16])NC=3C=2)[C:5](F)=[CH:4][N:3]=1.[CH3:20][N:21]1[CH2:26][CH2:25][N:24]([C:27]2[N:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH2:23][CH2:22]1.[C:34]([OH:40])([C:36](F)(F)F)=O.[CH3:41]C(O)C>>[CH3:41][C:5]1[C:6]([NH:8][C:9]2[CH:18]=[CH:17][C:12]3[NH:13][C:14](=[O:16])[O:40][C:34]=3[CH:36]=2)=[N:7][C:2]([NH:33][C:30]2[CH:31]=[N:32][C:27]([N:24]3[CH2:25][CH2:26][N:21]([CH3:20])[CH2:22][CH2:23]3)=[CH:28][CH:29]=2)=[N:3][CH:4]=1

Participants

5

Reactant 4

HCID 3776IsopropanolHCID 6422Trifluoroacetic acidHCID 27633906-(4-Methylpiperazin-1-yl)pyridin-3-amineHCID 866436435-(2-Chloro-5-fluoropyrimidin-4-ylamino)-1H-benzo[d]imidazol-2(3H)-one

Product 1

HCID 666594856-(5-Methyl-2-(6-(4-methylpiperazin-1-yl)pyridin-3-ylamino)pyrimidin-4-ylamino)benzo[d]oxazol-2(3H)-oneYield 60%

Conditions

Temperature
85 °C

Procedure

To a vial with 5-(2-chloro-5-fluoropyrimidin-4-ylamino)-1H-benzo[d]imidazol-2(3H)-one (28.0 mg, 0.1 mmol) and 6-(4-methylpiperazin-1-yl)pyridin-3-amine (38.4 mg, 0.2 mmol), i-PrOH (2 mL) was added, followed by TFA (10 μL, 0.13 mmol). The vial was tightly closed, and the solution was stirred at 85° C. for 2 days. The solvent was removed in vacuo, and the crude product was purified by RP-HPLC. Purified compound (as a trifluoroacetate salt) was dissolved in MeOH—H2O (1:4, 2 mL) and was passed through a PL-HCO3-MP-SPE column, washing with same solvents (1 mL). The filtrate was collected and the solvent was removed by lyophilization. 6-(5-Methyl-2-(6-(4-methylpiperazin-1-yl)pyridin-3-ylamino)pyrimidin-4-ylamino)benzo[d]oxazol-2(3H)-one was obtained as a purple solid: 26.2 mg (60% yield); 1H NMR (300 MHz, DMSO) δ 11.70 (s, 1H), 9.97 (s, 1H), 9.49 (s, 1H), 8.15 (s, 1H), 7.82 (s, 1H), 7.65 (d, J=11.7, 2H), 7.21 (d, J=8.8, 1H), 7.05 (d, J=8.4, 1H), 6.89 (d, J=8.9, 1H), 4.34-4.31 (m, 4H), 3.09-3.07 (m, 4H), 2.85 (s, 3H), 2.13 (s, 3H).

Workup

  1. customThe vial was tightly closed
  2. customThe solvent was removed in vacuo
  3. customthe crude product was purified by RP-HPLC
  4. dissolutionPurified compound (as a trifluoroacetate salt) was dissolved in MeOH—H2O (1:4, 2 mL)
  5. washwashing with same solvents (1 mL)
  6. customThe filtrate was collected
  7. customthe solvent was removed by lyophilization

Sources & evidence

ORD record
ord-f7bb2c299d234026a3c1e802e5e4c52b
Source dataset
uspto-grants-2013_09
Patent number
US08524901B2

Linked notes

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