Trifluoroacetic acid → N4-(Benzimidazolin-2-on-5-yl)-N2-[2-(4-methylpiperazin-1-yl)pyridin-5-yl]-5-fluoropyrimidine-2,4-diamine

HRID 39324

Reaktionsgleichung

Reaktionsgleichung von HRID 39324
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])[NH:15][C:11]=3[CH:10]=2)[C:5]([F:19])=[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(O)(C(F)(F)F)=O>CC(O)C>[NH:13]1[C:12]2[CH:17]=[CH:18][C:9]([NH:8][C:6]3[C:5]([F:19])=[CH:4][N:3]=[C:2]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([N:24]5[CH2:25][CH2:26][N:21]([CH3:20])[CH2:22][CH2:23]5)=[N:32][CH:31]=4)[N:7]=3)=[CH:10][C:11]=2[NH:15][C:14]1=[O:16]

Komponenten

5

Edukt 3

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

Produkt 1

HCID 66659567N4-(Benzimidazolin-2-on-5-yl)-N2-[2-(4-methylpiperazin-1-yl)pyridin-5-yl]-5-fluoropyrimidine-2,4-diamineAusbeute 60 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 3776IsopropanolLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

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. N4-(Benzimidazolin-2-on-5-yl)-N2-[2-(4-methylpiperazin-1-yl)pyridin-5-yl]-5-fluoropyrimidine-2,4-diamine was obtained as a purple solid: 26.2 mg (60% yield); 1H NMR (300 MHz, DMSO) δ 10.56 (s, 1H), 10.52 (s, 1H), 9.16 (s, 1H), 8.85 (s, 1H), 8.27 (br d, J=2.3, 1H), 8.00 (br d, J=3.8, 1H), 7.84 (dd, J=2.3, 9.1, 1H), 7.30 (dd, J=1.7, 8.2, 1H), 7.17 (d, J=1.7, 1H), 6.86 (d, J=8.2, 1H), 6.73 (d, J=9.1, 1H), 3.40-3.37 (m, 4H, overlapped with H2O), 2.44-2.41 (m, 4H), 2.25 (s, 3H); LCMS (M+) m/z 436.50.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-86c7309d4b45437fb2658a703b705477
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08524901B2

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