Diisopropylethylamine → 1-[4-[2-(difluoromethyl)-4-methoxybenzimidazol-1-yl]-6-morpholin-4-yl-1,3,5-triazin-2-yl]-N,N-dimethylpiperidine-4-sulfonamide

HRID 1256562노트

반응식

HRID 1256562 반응식
[CH3:1][N:2]([CH3:22])[S:3]([CH:6]1[CH2:11][CH2:10][N:9]([C:12](OCC2C=CC=CC=2)=O)[CH2:8][CH2:7]1)(=[O:5])=[O:4].ClC1[N:29]=[C:28]([N:30]2[CH2:35][CH2:34][O:33][CH2:32][CH2:31]2)[N:27]=[C:26]([N:36]2[C:40]3[CH:41]=[CH:42][CH:43]=[C:44]([O:45][CH3:46])[C:39]=3[N:38]=[C:37]2[CH:47]([F:49])[F:48])[N:25]=1.CCN(C(C)C)C(C)C>CO.C1COCC1.[Pd]>[F:49][CH:47]([F:48])[C:37]1[N:36]([C:26]2[N:27]=[C:28]([N:30]3[CH2:31][CH2:32][O:33][CH2:34][CH2:35]3)[N:29]=[C:12]([N:9]3[CH2:8][CH2:7][CH:6]([S:3]([N:2]([CH3:1])[CH3:22])(=[O:4])=[O:5])[CH2:11][CH2:10]3)[N:25]=2)[C:40]2[CH:41]=[CH:42][CH:43]=[C:44]([O:45][CH3:46])[C:39]=2[N:38]=1

참가 물질

7

반응물 3

HCID 81531DiisopropylethylamineHCID 534881021-[4-Chloro-6-(morpholin-4-yl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-4-methoxy-1H-benzimidazoleHCID 53587548Benzyl 4-[(dimethylamino)sulfonyl]-1-piperidinecarboxylate

생성물 1

HCID 469175741-[4-[2-(difluoromethyl)-4-methoxybenzimidazol-1-yl]-6-morpholin-4-yl-1,3,5-triazin-2-yl]-N,N-dimethylpiperidine-4-sulfonamide수율 86%

시약·촉매·용매 3

HCID 23938Palladium촉매HCID 887Methanol용매HCID 8028Tetrahydrofuran용매

실험 절차

The above carbamate was hydrogenated over 5% Pd on carbon in MeOH. After removal of the solvent, the residue was combined with 0.19 g (0.48 mmol) 1-[4-chloro-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-4-methoxy-1H-benzimidazole (Example 2) and DIPEA in THF. The mixture was heated under reflux for 30 min and the solvent was removed. After dilution with water, the resulting solid was collected and dried. Chromatography on silica, eluting with CH2Cl2/EtOAc (93:7), gave 0.227 g (86% yield) of 1-[4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-N,N-dimethyl-4-piperidinesulfonamide: mp (MeOH) 260-264° C.; 1H NMR (CDCl3) δ 7.88 (dd, J=8.4, 0.6 Hz, 1H), 7.46 (t, JHF=53.5 Hz, 1H), 7.35 (t, J=7.7 Hz, 1H), 6.81 (d, J=7.7 Hz, 1H), 4.91 (br d, J=13.5 Hz, 2H), 4.05 (s, 3H), 3.88 (m, 4H), 3.78 (m, 4H), 3.27 (tt, J=11.8, 3.8 Hz, 1H), 2.95 (s, 6H), 2.17 (dd, J=12.7, 2.2 Hz, 2H), 1.85 (dq, J=12.6, 4.2 Hz, 2H); Anal. Calcd. for C23H30F2N8O4S: C, 50.0; H, 5.5; N, 20.3. Found: C, 49.9; H, 5.5; N, 20.4%.

후처리

  1. customAfter removal of the solvent
  2. temperatureThe mixture was heated
  3. temperatureunder reflux for 30 min
  4. customthe solvent was removed
  5. customAfter dilution with water, the resulting solid was collected
  6. customdried
  7. washChromatography on silica, eluting with CH2Cl2/EtOAc (93:7)

출처 및 근거

ORD 기록
ord-ac17e610ede74c4188a9ef74df97a40d
출처 데이터셋
uspto-grants-2013_06
특허 번호
US08461158B2

반응 노트

불러오는 중…