Trifluoroacetic acid → (R)-N-(3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)pyridin-2-yl)-5-fluoroquinolin-7-amine

HRID 1812250노트

반응식

HRID 1812250 반응식
COC1C=CC(C[N:8](CC2C=CC(OC)=CC=2)[C:9]2[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([C:16]3[C:17]([NH:34][C:35]4[CH:44]=[C:43]5[C:38]([CH:39]=[CH:40][CH:41]=[N:42]5)=[C:37]([F:45])[CH:36]=4)=[N:18][CH:19]=[C:20]([C@H:22]([N:24]4[CH2:29][CH2:28][N:27]([S:30]([CH3:33])(=[O:32])=[O:31])[CH2:26][CH2:25]4)[CH3:23])[CH:21]=3)[N:10]=2)=CC=1.FC(F)(F)C(O)=O>>[NH2:8][C:9]1[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([C:16]2[C:17]([NH:34][C:35]3[CH:44]=[C:43]4[C:38]([CH:39]=[CH:40][CH:41]=[N:42]4)=[C:37]([F:45])[CH:36]=3)=[N:18][CH:19]=[C:20]([C@H:22]([N:24]3[CH2:25][CH2:26][N:27]([S:30]([CH3:33])(=[O:31])=[O:32])[CH2:28][CH2:29]3)[CH3:23])[CH:21]=2)[N:10]=1

참가 물질

3

반응물 2

HCID 6422Trifluoroacetic acidHCID 66611412HCID 66611412, 화합물

생성물 1

HCID 59548193(R)-N-(3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)pyridin-2-yl)-5-fluoroquinolin-7-amine수율 58.2%

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온도
75 °C

실험 절차

A glass microwave reaction vessel was charged with (R)-N-(3-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-5-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)pyridin-2-yl)-5-fluoroquinolin-7-amine (82 mg, 0.105 mmol) and trifluoroacetic acid (1 mL, 13.46 mmol, Aldrich). The reaction mixture was stirred and heated in an oil bath at 75° C. for 14 h. The solvent was removed in vacuo. The residue was treated with 10% MeOH/CH2Cl2 (40 mL). The reaction mixture was washed with sat. NaHCO3 (10 mL), saturated NaCl (10 mL) and dried over Na2SO4. The solution was filtered and concentrated in vacuo to give the crude material as a yellow solid. The crude product was purified by silica gel chromatography eluting with 5% MeOH/CH2Cl2 to give (R)-N-(3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)pyridin-2-yl)-5-fluoroquinolin-7-amine (33 mg, 0.061 mmol, 58.2% yield). 1H NMR (300 MHz, CDCl3) δ 1.47 (d, J=6.72 Hz, 3H) 2.52-2.72 (m, 7H) 2.78 (s, 3H) 3.25 (t, J=4.17 Hz, 4H) 3.60 (q, J=6.53 Hz, 1H) 5.49 (s, 2H) 7.12-7.24 (m, 1H) 7.39-7.54 (m, 1H) 7.83 (d, J=8.33 Hz, 1H) 8.48 (d, J=2.19 Hz, 1H) 8.77 (d, J=2.05 Hz, 1H) 8.96 (d, J=2.34 Hz, 1H) 9.25 (d, J=1.90 Hz, 1H) 12.51 (s, 1H). m/z (ESI, +ve ion) 538.1 (M+H)+.

후처리

  1. customA glass microwave reaction vessel
  2. customThe solvent was removed in vacuo
  3. additionThe residue was treated with 10% MeOH/CH2Cl2 (40 mL)
  4. washThe reaction mixture was washed with sat. NaHCO3 (10 mL), saturated NaCl (10 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationThe solution was filtered
  7. concentrationconcentrated in vacuo
  8. customto give the crude material as a yellow solid
  9. customThe crude product was purified by silica gel chromatography
  10. washeluting with 5% MeOH/CH2Cl2

출처 및 근거

ORD 기록
ord-9eee5e8fdd524ee08b41665f29abc93e
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08362241B2

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