Dimethylacetamide → ethyl 3-((6-chloro-2-cyano-1-(1-propyl-1H-pyrazol-4-yl)-1H-indol-3-yl)thio)benzoate

HRID 522756ノート

反応式

HRID 522756 の反応式
Br[C:2]1[N:3]([C:24]2[CH:25]=[N:26][N:27]([CH2:29][CH2:30][CH3:31])[CH:28]=2)[C:4]2[C:9]([C:10]=1[S:11][C:12]1[CH:13]=[C:14]([CH:20]=[CH:21][CH:22]=1)[C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:8][CH:7]=[C:6]([Cl:23])[CH:5]=2.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C[C:75]([N:77](C)C)=O>O.[Zn].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:23][C:6]1[CH:5]=[C:4]2[C:9]([C:10]([S:11][C:12]3[CH:13]=[C:14]([CH:20]=[CH:21][CH:22]=3)[C:15]([O:17][CH2:18][CH3:19])=[O:16])=[C:2]([C:75]#[N:77])[N:3]2[C:24]2[CH:25]=[N:26][N:27]([CH2:29][CH2:30][CH3:31])[CH:28]=2)=[CH:8][CH:7]=1

参加物

7

反応物 3

HCID 31374DimethylacetamideHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 118094237ethyl 3-((2-bromo-6-chloro-1-(1-propyl-1H-pyrazol-4-yl)-1H-indol-3-yl)thio)benzoate

生成物 1

HCID 118094311ethyl 3-((6-chloro-2-cyano-1-(1-propyl-1H-pyrazol-4-yl)-1H-indol-3-yl)thio)benzoate収率 33%

試薬・触媒・溶媒 3

HCID 23994Zinc触媒HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒

反応条件

温度
120 °C

実験手順

To a stirred solution of compound 4 (200 mg, 0.38 mmol) in DMA (20 mL) under inert atmosphere were added zinc powder (5.02 mg, 0.07 mmol), ZnCN2 (67.8 mg, 0.58 mmol), xantphos (89.5 mg, 0.15 mmol), Pd2(dba)3 (70.85 mg, 0.07 mmol) at RT; heated to 120° C. under microwave for 30 min. The reaction was monitored by TLC; after completion of the reaction, the reaction mixture was diluted with water (20 mL) and extracted with CH2Cl2 (3×20 mL). The combined organic extracts were dried over Na2SO4, filtered and concentrated under reduced pressure to obtain the crude. This was purified by silica gel column chromatography using 10-15% EtOAc/Hexanes to afford compound 5 (60 mg, 33%) as an off-white solid. 1H NMR (500 MHz, CDCl3): δ 7.99 (s, 1H), 7.87 (d, J=7.5 Hz, 1H), 7.78 (s, 2H), 7.54 (d, J=8.5 Hz, 1H), 7.42-7.27 (m, 3H), 7.24-7.22 (m, 1H), 4.36 (q, J=7.0 Hz, 2H), 4.21 (t, J=7.5 Hz, 2H), 2.02-1.98 (m, 2H), 1.36 (t, J=7.0 Hz, 3H), 1.01 (t, J=7.5 Hz, 3H); LC-MS (ESI): 92.5%; m/z 465 (M+H+); (column: X Select CSH C-18, 50×3.0 mm, 3.5 μm); RT 4.92 min; 5 mM NH4OAc: ACN; 0.8 mL/min).

後処理

  1. customafter completion of the reaction
  2. extractionextracted with CH2Cl2 (3×20 mL)
  3. dry with materialThe combined organic extracts were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customto obtain the crude
  7. customThis was purified by silica gel column chromatography

出典と根拠

ORDレコード
ord-a029630f116243d9a87281b749012f7f
出典データセット
uspto-grants-2016_05
特許番号
US09334261B2

反応ノート

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