Nitrogen → N-benzyl-2-methoxy-5-(2-methyl-1-oxoisoquinolin-4-yl)benzamide

HRID 575545Notes

Reaction equation

HRID 575545 reaction equation
N#N.[CH2:3]([NH:10][C:11](=[O:29])[C:12]1[CH:17]=[C:16](B2OC(C)(C)C(C)(C)O2)[CH:15]=[CH:14][C:13]=1[O:27][CH3:28])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Br[C:31]1[C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[C:34](=[O:41])[N:33]([CH3:42])[CH:32]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH2:3]([NH:10][C:11](=[O:29])[C:12]1[CH:17]=[C:16]([C:31]2[C:40]3[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=3)[C:34](=[O:41])[N:33]([CH3:42])[CH:32]=2)[CH:15]=[CH:14][C:13]=1[O:27][CH3:28])[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

7

Reactant 4

HCID 947NitrogenHCID 62657Potassium Phosphate, TribasicHCID 3118584-Bromo-2-methylisoquinolin-1(2H)-oneHCID 123789009N-Benzyl-2-methoxy-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzamide

Product 1

HCID 118022338N-benzyl-2-methoxy-5-(2-methyl-1-oxoisoquinolin-4-yl)benzamideYield 107.7%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Procedure

For about 3 min, N2 was bubbled through a mixture of N-benzyl-2-methoxy-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (51 mg, 0.14 mmol), 4-bromo-2-methylisoquinolin-1(2H)-one (30 mg, 0.13 mmol), aqueous 1M K3PO4 (0.3 mL) and Pd(dppf)Cl2 (10 mg, 0.013 mmol) in dioxane (1.15 mL) which was then microwaved at 100° C. for 1 h. Work up similar to Example 15 and purification by silica gel chromatography, eluting with 5-50% EA in hexane over 4 min and continuing 50% isocratic EA gave the title compound (37 mg, 0.14 mmol) as a tan solid in 71% yield. 1H NMR (400 MHz, DMSO-d6) δ 3.57 (s, 3H), 3.97 (s, 3H), 4.52 (d, J=6.06 Hz, 2H), 7.21-7.37 (m, 6H), 7.47-7.51 (m, 2H), 7.56 (td, J=5.37, 2.15 Hz, 2H), 7.68-7.73 (m, 1H), 7.79 (d, J=2.27 Hz, 1H), 8.33 (d, J=7.83 Hz, 1H), 8.79 (t, J=6.06 Hz, 1H). LCMS (M−H)+ 399.

Workup

  1. customwas then microwaved at 100° C. for 1 h
  2. customWork up similar to Example 15 and purification by silica gel chromatography
  3. washeluting with 5-50% EA in hexane over 4 min

Sources & evidence

ORD record
ord-1e6b8a796dd44885be771a6a2df95712
Source dataset
uspto-grants-2015_05
Patent number
US09034900B2

Reaction notes

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