Potassium Phosphate, Tribasic → HCID 57493288, compound

HRID 1890748Notes

Reaction equation

HRID 1890748 reaction equation
[NH2:1][C:2]1[CH:3]=[N:4][C:5]([CH3:17])=[C:6]([CH:16]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:8].Br[C:19]1[CH:28]=[CH:27][CH:26]=[C:25]2[C:20]=1[CH2:21][CH2:22][N:23]([S:29]([CH3:32])(=[O:31])=[O:30])[CH2:24]2.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.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]>[CH3:17][C:5]1[N:4]=[CH:3][C:2]([NH:1][C:19]2[CH:28]=[CH:27][CH:26]=[C:25]3[C:20]=2[CH2:21][CH2:22][N:23]([S:29]([CH3:32])(=[O:31])=[O:30])[CH2:24]3)=[CH:16][C:6]=1[C:7]([NH:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:8]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 634876Binap, (A+-)-HCID 58317894HCID 58317894, compoundHCID 58318096HCID 58318096, compound

Product 1

HCID 57493288HCID 57493288, compound

Reagents, catalysts & solvents 2

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

Conditions

Temperature
110 °C

Procedure

A mixture containing 5-amino-2-methyl-N-phenylnicotinamide (46 mg, 0.2 mmol), 5-bromo-2-(methylsulfonyl)-1,2,3,4-tetrahydroisoquinoline (58 mg, 0.2 mmol), Pd2(dba)3 (18 mg, 0.02 mmol), BINAP (25 mg, 0.04 mmol), K3PO4 (169 mg, 0.8 mmol) in dioxane (1 mL) is stirred at 110° C. for 15 hours. The reaction mixture is filtered through a celite pad to remove any solids. The filtrate is evaporated and the crude product is purified by HPLC to give 2-methyl-5-(2-(methylsulfonyl)-1,2,3,4-tetrahydroisoquinolin-5-ylamino)-N-phenylnicotinamide as a white solid. MS m/z 437.2 (M+1); 1H NMR 400 MHz (DMSO-d6) δ10.58 (s, 1H), 8.20 (m, 2H), 7.71 (d, 2H, J=7.6 Hz), 7.63 (d, 1H), J=2.4 Hz), 7.38 (t, 2H, J=8.4 Hz), 7.23 (m, 2H), 7.15 (t, 1H, J=7.6 Hz), 7.00 (m, 1H), 4.39 (s, 2H), 3.47 (t, 2H, J=6.4 Hz), 2.97 (s, 3H), 2.82 (t, 2H, J=6.4 Hz), 2.54 (s, 3H).

Workup

  1. filtrationThe reaction mixture is filtered through a celite pad
  2. customto remove any solids
  3. customThe filtrate is evaporated
  4. customthe crude product is purified by HPLC

Sources & evidence

ORD record
ord-ccd8d4c9db6140a2afe73c81858eab6e
Source dataset
uspto-grants-2013_08
Patent number
US08507491B2

Reaction notes

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