Chlorosuccinimide → methyl 6-((6-chloro-2-cyclopropyl-1-(1-ethyl-1H-pyrazol-4-yl)-7-fluoro-1H-indol-3-yl)thio)picolinate

HRID 2171303ノート

反応式

HRID 2171303 の反応式
[SH:1][C:2]1[N:7]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[CH:5]=[CH:4][CH:3]=1.C1C(=O)N(Cl)C(=O)C1.[Cl:20][C:21]1[C:29]([F:30])=[C:28]2[C:24]([CH:25]=[C:26]([CH:38]3[CH2:40][CH2:39]3)[N:27]2[C:31]2[CH:32]=[N:33][N:34]([CH2:36][CH3:37])[CH:35]=2)=[CH:23][CH:22]=1>C(Cl)Cl>[Cl:20][C:21]1[C:29]([F:30])=[C:28]2[C:24]([C:25]([S:1][C:2]3[N:7]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[CH:5]=[CH:4][CH:3]=3)=[C:26]([CH:38]3[CH2:40][CH2:39]3)[N:27]2[C:31]2[CH:32]=[N:33][N:34]([CH2:36][CH3:37])[CH:35]=2)=[CH:23][CH:22]=1

参加物

5

反応物 3

HCID 31398ChlorosuccinimideHCID 1181041966-chloro-2-cyclopropyl-1-(1-ethyl-1H-pyrazol-4-yl)-7-fluoro-1H-indoleHCID 178498017HCID 178498017、化合物

生成物 1

HCID 118104201methyl 6-((6-chloro-2-cyclopropyl-1-(1-ethyl-1H-pyrazol-4-yl)-7-fluoro-1H-indol-3-yl)thio)picolinate収率 32.2%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒3 回

実験手順

To a stirred solution of methyl 6-mercaptopicolinate 6 (3.15 g, crude) in CH2Cl2 (50 mL) under inert atmosphere was added NCS (2.49 g, 18.63 mmol) at RT and stirred for 1 h. To this, indole 5 (5.6 g, 18.47 mmol) in CH2Cl2 (50 mL) was added at RT and stirred for 16 h. After completion of the reaction (TLC), the reaction mixture was diluted CH2Cl2 (100 mL) washed with water (3×100 mL). The organic extract was dried over Na2SO4, filtered and concentrated under reduced pressure to obtain the crude. The crude was purified (silica gel column chromatography; 10% EtOAc/hexanes) to afford 9 (2.8 g, 32%) as a pale brown solid. 1H NMR (500 MHz, DMSO-d6): δ 7.79 (d, J=7.5 Hz, 1H), 7.66 (d, J=10.5 Hz, 2H), 7.51 (t, J=7.5 Hz, 1H), 7.19 (d, J=8.5 Hz, 1H), 7.10-7.07 (m, 1H), 6.78 (d, J=8.0 Hz, 1H), 4.28 (q, 2H), 4.00 (s, 3H), 1.75-1.69 (m, 1H), 1.58 (t, J=7.0 Hz, 3H), 1.09-1.08 (m, 2H), 0.87-0.84 (m, 2H); LC-MS: 98.4%; m/z 471.4 (M+H+);(column; X-select CSH C-18, (50×3.0 mm, 3.5 μm); RT 4.25 min. 5.0 mM NH4OAc (Aq): ACN; 0.8 mL/min); HPLC: 98.1%; (column: Acquity BEH C-18 (50×2.1 mm, 1.7μ); RT 3.02 min. ACN: 0.025% TFA (aq); 0.5 mL/min).

後処理

  1. stirringstirred for 16 h
  2. customAfter completion of the reaction (TLC)
  3. washwashed with water (3×100 mL)
  4. extractionThe organic extract
  5. dry with materialwas dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto obtain the crude
  9. customThe crude was purified (silica gel column chromatography; 10% EtOAc/hexanes)

出典と根拠

ORDレコード
ord-14f01761c5f94071afae37f992f2c59b
出典データセット
uspto-grants-2015_06
特許番号
US09051320B1

反応ノート

読み込み中…