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

HRID 39323노트

반응식

HRID 39323 반응식
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:10]=[CH:11][C:12]3[O:16][C:15](=[O:17])[NH:14][C:13]=3[CH:18]=2)[C:5]([CH3:19])=[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>C(O)CC>[O:16]1[C:12]2[CH:11]=[CH:10][C:9]([NH:8][C:6]3[C:5]([CH3:19])=[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:18][C:13]=2[NH:14][C:15]1=[O:17]

참가 물질

5

반응물 3

HCID 6422Trifluoroacetic acidHCID 27633906-(4-Methylpiperazin-1-yl)pyridin-3-amineHCID 580713875-(2-Chloro-5-methylpyrimidin-4-ylamino)benzo[d]oxazol-2(3H)-one

생성물 1

HCID 66659601N4-(benzoxazolin-2-on-5-yl)-N2-[2-(4-methylpiperazin-1-yl)pyridin-5-yl]-5-methylpyrimidine-2,4-diamine수율 53%

시약·촉매·용매 1

HCID 10311-Propanol용매

반응 조건

온도
85 °C

실험 절차

To a vial with 5-(2-chloro-5-methylpyrimidin-4-ylamino)benzo[d]oxazol-2(3H)-one (27.7 mg, 0.5 mmol) and 6-(4-methylpiperazin-1-yl)pyridin-3-amine (38.4 mg, 1.0 mmol), PrOH (2 mL) was added, followed by TFA (10 μL, 0.13 mmol). The vial was tightly closed, and the reaction mixture was stirred at 85° C. for 2 days. The solvents were 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-(benzoxazolin-2-on-5-yl)-N2-[2-(4-methylpiperazin-1-yl)pyridin-5-yl]-5-methylpyrimidine-2,4-diamine was obtained as a purple solid, 23.1 mg (53% yield); 1H NMR (300 MHz, DMSO) δ 11.57 (s, 1H), 8.73 (s, 1H), 8.30-8.28 (m, 2H), 7.87-7.84 (m, 2H), 7.46-7.28 (m, 2H), 7.22 (d, J=8.5, 1H), 6.71 (d, J=9.1, 1H), 3.40-3.37 (m, 4H, overlapped with H2O), 2.44-2.41 (m, 4H), 2.25 (s, 3H), 2.11 (s, 3H); LCMS (M+) m/z 433.52.

후처리

  1. customThe vial was tightly closed
  2. customThe solvents were 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

출처 및 근거

ORD 기록
ord-167f2120e754446ca16314290405fec5
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08524901B2

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