Potassium Phosphate, Tribasic → [2-(1,1-Dioxo-tetrahydro-thiophen-3-yl)-1,2,3,4-tetrahydro-isoquinolin-5-yl]-[3-(6-methoxy-pyridazin-3-yl)-4-methyl-phenyl]-amine

HRID 1890750

反応式

HRID 1890750 の反応式
Br[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][N:6]([CH:12]1[CH2:16][CH2:15][S:14](=[O:18])(=[O:17])[CH2:13]1)[CH2:7]2.[CH3:19][O:20][C:21]1[N:26]=[N:25][C:24]([C:27]2[CH:28]=[C:29]([CH:31]=[CH:32][C:33]=2[CH3:34])[NH2:30])=[CH:23][CH:22]=1.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.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>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].O1CCOCC1>[O:17]=[S:14]1(=[O:18])[CH2:15][CH2:16][CH:12]([N:6]2[CH2:5][CH2:4][C:3]3[C:8](=[CH:9][CH:10]=[CH:11][C:2]=3[NH:30][C:29]3[CH:31]=[CH:32][C:33]([CH3:34])=[C:27]([C:24]4[N:25]=[N:26][C:21]([O:20][CH3:19])=[CH:22][CH:23]=4)[CH:28]=3)[CH2:7]2)[CH2:13]1

参加物

7

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 583178905-Bromo-2-(1,1-dioxo-tetrahydro-thiophen-3-yl)-1,2,3,4-tetrahydro-isoquinolineHCID 672124083-(6-Methoxypyridazin-3-yl)-4-methylaniline

生成物 1

HCID 57493300[2-(1,1-Dioxo-tetrahydro-thiophen-3-yl)-1,2,3,4-tetrahydro-isoquinolin-5-yl]-[3-(6-methoxy-pyridazin-3-yl)-4-methyl-phenyl]-amine

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

To the reaction vessel containing 5-Bromo-2-(1,1-dioxo-tetrahydro-thiophen-3-yl)-1,2,3,4-tetrahydro-isoquinoline (460 mg, 1.4 mmol), 3-(6-methoxypyridazin-3-yl)-4-methylaniline (300 mg, 1.4 mmol), Pd2(dba)3 (128 mg, 0.14 mmol), Xantphos (162 mg, 0.28 mmol) and K3PO4 (740 mg, 3.5 mmol) is added anhydrous dioxane. The vessel is flushed with nitrogen, sealed and heated to 100° C. for 15 hours. The reaction is then cooled to ambient temperature, filtered through a celite pad to remove any solids. The filtrate is concentrated and purified by silica gel flash chromatography to afford [2-(1,1-dioxo-tetrahydro-thiophen-3-yl)-1,2,3,4-tetrahydro-isoquinolin-5-yl]-[3-(6-methoxy-pyridazin-3-yl)-4-methyl-phenyl]-amine as an off-white solid. MS m/z 465.2 (M+1); 1H NMR 400 MHz (DMSO-d6) δ7.73 (d, 1H, J=6.0 Hz), 7.32 (s, 1H), 7.27 (d, 1H, J=6.0 Hz), 7.16 (d, 1H, J=5.6 Hz), 7.04 (m, 2H), 6.95 (m, 2H), 6.69 (dd, 1H, J1=4.4 Hz, J2=2.8 Hz), 4.07 (s, 3H), 3.72 (d, 1H, J=15.0 Hz), 3.65 (d, 1H, J=15.0 Hz), 3.41 (m, 2H), 3.29 (m, 1H), 3.13 9 m, 2H), 2.77 (m, 2H), 2.66 (t, 2H, J=6.0 Hz), 2.43 (m, 1H), 2.18 (s, 3H), 2.11 (m, 1H).

後処理

  1. customThe vessel is flushed with nitrogen
  2. customsealed
  3. temperatureThe reaction is then cooled to ambient temperature
  4. filtrationfiltered through a celite pad
  5. customto remove any solids
  6. concentrationThe filtrate is concentrated
  7. custompurified by silica gel flash chromatography

出典と根拠

ORDレコード
ord-138c2f4adf0248e7ba359ed46e71dc2d
出典データセット
uspto-grants-2013_08
特許番号
US08507491B2

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