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 1505062

반응식

HRID 1505062 반응식
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

참가 물질

7

반응물 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

생성물 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

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 312751,4-Dioxane용매

반응 조건

온도
100 °C

실험 절차

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) δ 7.73 (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 9m, 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).

후처리

  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

출처 및 근거

ORD 기록
ord-de65c60da5b44d19bef0db58c9597167
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09216964B2

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