Potassium Phosphate, Tribasic → 6-benzyl-N-(3-(isoquinolin-3-yl)-4-methylphenyl)-5,6,7,8-tetrahydro-2,6-naphthyridin-1-amine

HRID 1890755Notes

Reaction equation

HRID 1890755 reaction equation
[CH2:1]([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[N:13][C:14]=2Br)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:19]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH:22]=[C:21]([C:29]2[CH:30]=[C:31]([CH:33]=[CH:34][C:35]=2[CH3:36])[NH2:32])[N:20]=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>[CH2:1]([N:8]1[CH2:17][CH2:16][C:15]2[C:14]([NH:32][C:31]3[CH:33]=[CH:34][C:35]([CH3:36])=[C:29]([C:21]4[N:20]=[CH:19][C:28]5[C:23]([CH:22]=4)=[CH:24][CH:25]=[CH:26][CH:27]=5)[CH:30]=3)=[N:13][CH:12]=[CH:11][C:10]=2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 223354025-Bromo-1,2,3,4-tetrahydro-2-(phenylmethyl)-2,6-naphthyridineHCID 583178853-(Isoquinolin-3-yl)-4-methylaniline

Product 1

HCID 583180566-benzyl-N-(3-(isoquinolin-3-yl)-4-methylphenyl)-5,6,7,8-tetrahydro-2,6-naphthyridin-1-amine

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

To the reaction vessel containing 2-benzyl-5-bromo-1,2,3,4-tetrahydro-2,6-naphthyridine (272 mg, 0.9 mmol), 3-(isoquinolin-3-yl)-4-methylaniline (210 mg, 0.9 mmol), Pd2(dba)3 (41 mg, 0.045 mmol), Xantphos (52 mg, 0.09 mmol) and K3PO4 (477 mg, 2.25 mmol) is added anhydrous dioxane (5 mL). The vessel is flushed with nitrogen, sealed and heated to 100° C. for 18 hours. The reaction is then cooled to ambient temperature, filtered through a celite pad to remove any salts. The filtrate is concentrated and purified by silica gel flash chromatography to afford 6-benzyl-N-(3-(isoquinolin-3-yl)-4-methylphenyl)-5,6,7,8-tetrahydro-2,6-naphthyridin-1-amine as an off-white solid. MS m/z 457.2 (M+1).

Workup

  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 salts
  6. concentrationThe filtrate is concentrated
  7. custompurified by silica gel flash chromatography

Sources & evidence

ORD record
ord-91a71171fb6c4e11afaef8f73e00f7d0
Source dataset
uspto-grants-2013_08
Patent number
US08507491B2

Reaction notes

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