Potassium Phosphate, Tribasic → N-(3-(Isoquinolin-3-yl)-4-methylphenyl)-2-(1,1-dioxo-thietan-3-yl)-1,2,3,4-tetrahydroisoquinolin-5-amine

HRID 1890735Notes

Reaction equation

HRID 1890735 reaction equation
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[CH2:15][S:14](=[O:17])(=[O:16])[CH2:13]1)[CH2:7]2.[CH:18]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH:21]=[C:20]([C:28]2[CH:29]=[C:30]([CH:32]=[CH:33][C:34]=2[CH3:35])[NH2:31])[N:19]=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>[CH:18]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH:21]=[C:20]([C:28]2[CH:29]=[C:30]([NH:31][C:2]3[C:3]4[CH2:4][CH2:5][N:6]([CH:12]5[CH2:15][S:14](=[O:17])(=[O:16])[CH2:13]5)[CH2:7][C:8]=4[CH:9]=[CH:10][CH:11]=3)[CH:32]=[CH:33][C:34]=2[CH3:35])[N:19]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 583178853-(Isoquinolin-3-yl)-4-methylanilineHCID 583179675-Bromo-2-(1,1-dioxo-thietan-3-yl)-1,2,3,4-tetrahydroisoquinoline

Product 1

HCID 57493327N-(3-(Isoquinolin-3-yl)-4-methylphenyl)-2-(1,1-dioxo-thietan-3-yl)-1,2,3,4-tetrahydroisoquinolin-5-amineYield 37%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
96 °C

Procedure

To a reaction tube under argon containing 5-bromo-2-(1,1-dioxo-thietan-3-yl)-1,2,3,4-tetrahydroisoquinoline (70 mg, 0.22 mmol), 3-(isoquinolin-3-yl)-4-methylaniline (51 mg, 0.22 mmol), Pd2(dba)3 (22 mg, 0.022 mmol), xantphos (37 mg, 0.044 mmol), potassium phosphate (133 mg, 0.66 mmol) is added anhydrous dioxane (1 ml). The mixture is stirred at 96° C. for 18 hours, cooled to room temperature, filtered through a celite pad to remove solid. The filtrate is concentrated and purified by preparative HPLC to afford N-(3-(Isoquinolin-3-yl)-4-methylphenyl)-2-(1,1-dioxo-thietan-3-yl)-1,2,3,4-tetrahydroisoquinolin-5-amine as a white solid (36.2 mg, 37%). LC-MS m/z: 470.2 (M+1); 1H NMR 400 MHz (CDCl3) δ9.31 (s, 1H), 8.00 (d, 2H, J=8.4), 7.83 (d, 1H, J=8.4 Hz), 7.72-7.70 (m, 2H), 7.61 (t, 1H, J=6.8 Hz), 7.20 (d, 1H, J=8.4 Hz), 7.13-7.09 (m, 3H), 6.94 (dd, 1H, J=2.4, 8.0 Hz), 6.70 (d, 1H, J=8.4 Hz), 5.34 (s, 1H), 4.44 (s, 2H), 3.59 (t, 2H, J=6.0 Hz), 2.97 (s, 3H), 2.82-2.78 (m, 6H), 2.34 (s, 3H).

Workup

  1. temperaturecooled to room temperature
  2. filtrationfiltered through a celite pad
  3. customto remove solid
  4. concentrationThe filtrate is concentrated
  5. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-f1fc53464c384432a7550cca4a41da16
Source dataset
uspto-grants-2013_08
Patent number
US08507491B2

Reaction notes

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