1-Methoxy-2-propanol → N-[2-(2-{4-[4-((R)-2-Hydroxy-propyl)-piperazin-1-yl]-phenylamino}-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-phenyl]-N-methyl-methanesulfonamide

HRID 1262030노트

반응식

HRID 1262030 반응식
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][C@H:15]([OH:17])[CH3:16])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.CS([C:21]1[N:26]=[CH:25][C:24]2=[CH:27][CH:28]=[C:29]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=3[N:36]([CH3:41])[S:37]([CH3:40])(=[O:39])=[O:38])[N:23]2[N:22]=1)=O.C(N(CC)C(C)C)(C)C.COCC(O)C>>[OH:17][C@H:15]([CH3:16])[CH2:14][N:11]1[CH2:10][CH2:9][N:8]([C:5]2[CH:4]=[CH:3][C:2]([NH:1][C:21]3[N:26]=[CH:25][C:24]4=[CH:27][CH:28]=[C:29]([C:30]5[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=5[N:36]([CH3:41])[S:37]([CH3:40])(=[O:39])=[O:38])[N:23]4[N:22]=3)=[CH:7][CH:6]=2)[CH2:13][CH2:12]1

참가 물질

5

반응물 4

HCID 79001-Methoxy-2-propanolHCID 81531DiisopropylethylamineHCID 28408103(2R)-1-[4-(4-Aminophenyl)piperazin-1-yl]propan-2-olHCID 54577677N-[2-(2-M ethanesulfinyl-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-phenyl]-N-methyl-methanesulfonamide

생성물 1

HCID 66710930N-[2-(2-{4-[4-((R)-2-Hydroxy-propyl)-piperazin-1-yl]-phenylamino}-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-phenyl]-N-methyl-methanesulfonamide수율 41.7%

실험 절차

(R)-1-[4-(4-Amino-phenyl)-piperazin-1-yl]-propan-2-ol (129.1 mg, 0.5488 mmol), N-[2-(2-Methanesulfinyl-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-phenyl]-N-methyl-methanesulfonamide (100.0 mg, 0.2744 mmol) and N,N-Diisopropylethylamine (0.1434 mL, 0.8232 mmol) were dissolved in 1-Methoxy-2-propanol (1.00 mL, 10.2 mmol). The reaction was irradiated at 300 watts, 200° C. for 20 minutes or until HPLC showed consumption of starting material. The mixture was then reduced under nitrogen and the product was isolated and purified by Gilson prep HPLC to afford 61.36 mg of N-[2-(2-{4-[4-((R)-2-Hydroxy-propyl)-piperazin-1-yl]-phenylamino}-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-phenyl]-N-methyl-methanesulfonamide as a lyophilized powder. (M+H)=536.1. 1H NMR (400 MHz, DMSO, d6) δ 9.51 (s, 1H), 9.24 (s, 1H), 8.95 (s, 1H), 8.01 (d, 1H, J=7.52 Hz), 7.65 (d, 1H, J=7.65 Hz), 7.50 (m, 4H), 6.97 (m, 2H), 6.85 (m, 2H), 4.12 (m, 1H), 3.66 (m, 4H), 3.17 (m, 3H), 3.08 (s, 3H), 2.95 (m, 3H), 2.89 (s, 3H), 1.13 (d, 3H, J=5.08 Hz).

후처리

  1. customThe reaction was irradiated at 300 watts, 200° C. for 20 minutes or until HPLC
  2. customconsumption of starting material
  3. customthe product was isolated
  4. custompurified by Gilson prep HPLC

출처 및 근거

ORD 기록
ord-20d2e4e2c0b046dea88d74ff70ac994e
출처 데이터셋
uspto-grants-2013_06
특허 번호
US08471005B2

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