Potassium Phosphate, Tribasic → 2-(2,2-Difluoropropyl)-N-(4-methyl-3-(5-methylpyridin-2-yl)phenyl)-1,2,3,4-tetrahydroisoquinolin-5-amine

HRID 1890733ノート

反応式

HRID 1890733 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]([CH2:12][C:13]([F:16])([F:15])[CH3:14])[CH2:7]2.[CH3:17][C:18]1[CH:24]=[CH:23][C:21]([NH2:22])=[CH:20][C:19]=1[C:25]1[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][N:26]=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.P([O-])([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>[F:15][C:13]([F:16])([CH3:14])[CH2:12][N:6]1[CH2:5][CH2:4][C:3]2[C:2]([NH:22][C:21]3[CH:23]=[CH:24][C:18]([CH3:17])=[C:19]([C:25]4[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][N:26]=4)[CH:20]=3)=[CH:11][CH:10]=[CH:9][C:8]=2[CH2:7]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 574932814-Methyl-3-(5-methylpyridin-2-yl)anilineHCID 583179355-Bromo-2-(2,2-difluoropropyl)-1,2,3,4-tetrahydroisoquinoline

生成物 1

HCID 583178822-(2,2-Difluoropropyl)-N-(4-methyl-3-(5-methylpyridin-2-yl)phenyl)-1,2,3,4-tetrahydroisoquinolin-5-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
96 °C

実験手順

To a reaction tube under argon containing 5-bromo-2-(2,2-difluoropropyl)-1,2,3,4-tetrahydroisoquinoline (29 mg, 0.1 mmol), 4-methyl-3-(5-methylpyridin-2-yl)aniline (20 mg, 0.1 mmol), Pd2(dba)3 (10 mg, 0.01 mmol), xantphos (17 mg, 0.02 mmol), potassium phosphate (60 mg, 0.3 mmol) is added anhydrous dioxane (0.5 ml). The mixture is stirred at 96° C. under argon for 18 hours, cooled to room temperature and filtered through a celite pad. The filtrate is concentrated and preparative HPLC is used to isolate 2-(2,2-Difluoropropyl)-N-(4-methyl-3-(5-methylpyridin-2-yl)phenyl)-1,2,3,4-tetrahydroisoquinolin-5-amine as a white solid. LC-MS m/z: 408.2 (M+1); 1H NMR 400 MHz (CDCl3) δ 8.48 (s, 1H), 7.52 (dd, 2H, J=1.6, 8 Hz), 7.28 (d, 1H, J=8.0 Hz), 7.14 (d, 1H, J=8.0 Hz), 7.07-7.00 (m, 2H), 6.95 (dd, 1H, J=2.4, 8.0 Hz), 6.62 (d, 1H, J=6.8 Hz), 5.30 (s, 1H), 3.77 (s, 2H), 2.92 (t, 2H, J=6.0 Hz), 2.83 (t, 2H, J=13.6 Hz), 2.66 (t, 2H, J=6.0 Hz), 2.36 (s, 3H), 2.27 (s, 3H), 1.66 (t, 3H, J=18.8 Hz).

後処理

  1. temperaturecooled to room temperature
  2. filtrationfiltered through a celite pad
  3. concentrationThe filtrate is concentrated

出典と根拠

ORDレコード
ord-c10e4ea597824bc7b675314ba36266cf
出典データセット
uspto-grants-2013_08
特許番号
US08507491B2

反応ノート

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