Potassium Phosphate, Tribasic → N-(3-methyl-2,2'-bipyridin-6-yl)-2-(2-(methylsulfonyl)ethyl)-1,2,3,4-tetrahydroisoquinolin-5-amine

HRID 1890745Notes

Reaction equation

HRID 1890745 reaction equation
[CH3:1][C:2]1[C:3]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=2)=[N:4][C:5]([NH2:8])=[CH:6][CH:7]=1.Br[C:16]1[CH:25]=[CH:24][CH:23]=[C:22]2[C:17]=1[CH2:18][CH2:19][N:20]([CH2:26][CH2:27][S:28]([CH3:31])(=[O:30])=[O:29])[CH2:21]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.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>[CH3:1][C:2]1[C:3]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=2)=[N:4][C:5]([NH:8][C:16]2[C:17]3[CH2:18][CH2:19][N:20]([CH2:26][CH2:27][S:28]([CH3:31])(=[O:30])=[O:29])[CH2:21][C:22]=3[CH:23]=[CH:24][CH:25]=2)=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 583180113-Methyl-2,2'-bipyridin-6-amineHCID 583180515-Bromo-2-(2-(methylsulfonyl)ethyl)-1,2,3,4-tetrahydroisoquinoline

Product 1

HCID 58318047N-(3-methyl-2,2'-bipyridin-6-yl)-2-(2-(methylsulfonyl)ethyl)-1,2,3,4-tetrahydroisoquinolin-5-amine

Reagents, catalysts & solvents 2

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

Conditions

Temperature
96 °C

Procedure

To a reaction tube under argon containing 3-methyl-2,2′-bipyridin-6-amine (20 mg, 0.11 mmol), 5-bromo-2-(2-(methylsulfonyl)ethyl)-1,2,3,4-tetrahydroisoquinoline (35 mg, 0.11 mmol), Pd2(dba)3 (11 mg, 0.011 mmol), xantphos (20 mg, 0.022 mmol), potassium phosphate (66 mg, 0.33 mmol) is added anhydrous dioxane (0.6 ml). The mixture is stirred at 96° C. for 18 hours, cooled to room temperature and filtered through a celite pad to remove any solids. The filtrate is concentrated and purified by preparative HPLC to afford N-(3-methyl-2,2′-bipyridin-6-yl)-2-(2-(methylsulfonyl)ethyl)-1,2,3,4-tetrahydroisoquinolin-5-amine as a white solid. LC-MS m/z: 423.2 (M+1); 1H NMR 400 MHz (CDCl3) δ 8.69 (d, 1H, J=5.2 Hz), 7.78 (td, 1H, J=1.6, 7.6 Hz), 7.68 (d, 1H, J=8.0 Hz), 7.39 (d, 1H, J=8.4 Hz), 7.32-7.24 (m, 3H), 7.13 (t, 1H, J=7.6 Hz), 6.79 (d, 1H, J=7.6 Hz), 6.72 (d, 1H, J=8.4 Hz), 6.19 (s, 1H), 3.69 (s, 2H), 3.22-3.20 (m, 2H), 3.03 (t, 2H, J=6.4 Hz), 2.99 (s, 3H), 2.80-2.74 (m, 4H), 2.32 (s, 3H).

Workup

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

Sources & evidence

ORD record
ord-b046be40551b4ab0becb46d6056df295
Source dataset
uspto-grants-2013_08
Patent number
US08507491B2

Reaction notes

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