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

HRID 1505057Notes

Reaction equation

HRID 1505057 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-85df99f91c9146a88510de8abc318d09
Source dataset
uspto-grants-2015_12
Patent number
US09216964B2

Reaction notes

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