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

HRID 516405ノート

反応式

HRID 516405 の反応式
[CH3:1][NH:2][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:28]=[C:27]([N:29]2[CH2:34][CH2:33][O:32][CH2:31][CH2:30]2)[N:26]=[C:25]([N:35]2[C:39]3[CH:40]=[CH:41][CH:42]=[C:43]([O:44][CH3:45])[C:38]=3[N:37]=[C:36]2[CH:46]([F:48])[F:47])[N:24]=1.CCN(C(C)C)C(C)C>CO.C1COCC1.[Pd]>[F:48][CH:46]([F:47])[C:36]1[N:35]([C:25]2[N:26]=[C:27]([N:29]3[CH2:30][CH2:31][O:32][CH2:33][CH2:34]3)[N:28]=[C:12]([N:9]3[CH2:8][CH2:7][CH:6]([S:3]([NH:2][CH3:1])(=[O:4])=[O:5])[CH2:11][CH2:10]3)[N:24]=2)[C:39]2[CH:40]=[CH:41][CH:42]=[C:43]([O:44][CH3:45])[C:38]=2[N:37]=1

参加物

7

反応物 3

HCID 81531DiisopropylethylamineHCID 534881021-[4-Chloro-6-(morpholin-4-yl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-4-methoxy-1H-benzimidazoleHCID 66698101benzyl 4-(N-methylsulfamoyl)piperidine-1-carboxylate

生成物 1

HCID 469175751-[4-[2-(difluoromethyl)-4-methoxybenzimidazol-1-yl]-6-morpholin-4-yl-1,3,5-triazin-2-yl]-N-methylpiperidine-4-sulfonamide収率 39%

試薬・触媒・溶媒 3

HCID 23938Palladium触媒HCID 887Methanol溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

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 concentrated. After dilution with water, the resulting solid was collected and dried. Chromatography on alumina, eluting with CH2Cl2/EtOAc (9:1), gave 0.127 g (39% yield) of 1-[4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-N-methyl-4-piperidinesulfonamide: mp (MeOH) 261-263° C.; 1H NMR (CDCl3) δ 7.87 (dd, J=8.4, 0.6 Hz, 1H), 7.46 (t, JHF=53.6 Hz, 1H), 7.35 (t, J=8.0 Hz, 1H), 6.82 (d, J=7.7 Hz, 1H), 4.93 (br d, J=13.5 Hz, 2H), 4.05 (s, 3H), 4.02 (q, J=5.3 Hz, 1H), 3.88 (m, 4H), 3.78 (m, 4H), 3.22 (tt, J=11.8, 3.7 Hz, 1H), 3.00 (m, 2H), 2.86 (d, J=5.3 Hz, 3H), 2.24 (br d, J=12.0 Hz, 2H), 1.85 (dq, J=12.5, 4.4 Hz, 2H); Anal. Calcd. for C22H28F2N8O4S: C, 49.1; H, 5.2; N, 20.8. Found: C, 49.2; H, 5.3; N, 21.0%.

後処理

  1. customAfter removal of the solvent
  2. temperatureThe mixture was heated
  3. temperatureunder reflux for 30 min
  4. concentrationthe solvent was concentrated
  5. customAfter dilution with water, the resulting solid was collected
  6. customdried
  7. washChromatography on alumina, eluting with CH2Cl2/EtOAc (9:1)

出典と根拠

ORDレコード
ord-1a7e0495ec4e42089c9c6e7da234f7af
出典データセット
uspto-grants-2015_08
特許番号
US09108980B2

反応ノート

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