Nitrogen → US10023592, Example 47

HRID 575555Notes

Reaction equation

HRID 575555 reaction equation
N#N.Br[C:4]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([F:14])[CH:12]=2)[C:7](=[O:15])[N:6]([CH3:16])[CH:5]=1.[CH3:17][S:18]([NH:21][C:22]1[CH:23]=[C:24](B(O)O)[CH:25]=[CH:26][CH:27]=1)(=[O:20])=[O:19].[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]>[F:14][C:11]1[CH:12]=[C:13]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:15])[N:6]([CH3:16])[CH:5]=[C:4]2[C:26]1[CH:27]=[C:22]([NH:21][S:18]([CH3:17])(=[O:19])=[O:20])[CH:23]=[CH:24][CH:25]=1

Participants

7

Reactant 4

HCID 947NitrogenHCID 62657Potassium Phosphate, TribasicHCID 27735353-Methylsulfonylaminophenylboronic acidHCID 1180215214-Bromo-6-fluoro-2-methylisoquinolin-1-one

Product 1

HCID 118021529US10023592, Example 47Yield 50%

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 4-bromo-6-fluoro-2-methylisoquinolin-1-one (41 mg, 0.16 mmol), (3-methanesulfonamidophenyl)boronic acid (38 mg, 0.18 mmol), aqueous 1 M K3PO4 (0.3 mL) and Pd(dppf)Cl2 (12 mg, 0.016 mmol) in dioxane (1.2 mL) which was then microwaved for 1 h at 120° C. Work up was similar to that described for Example 18, step 3. Purification using silica gel chromatography, eluting with 40-80% EA in hexane over 5 min and continuing 80% isocratic EA gave the title compound (28 mg, 0.08 mmol) as a cream solid in a combined yield of 38% over steps 1-3. 1H NMR (400 MHz, DMSO-d6) δ 3.06 (s, 3H), 3.56 (s, 3H), 7.15-7.22 (m, 2H), 7.25-7.31 (m, 2H), 7.41 (td, J=8.65, 2.65 Hz, 1H), 7.45-7.52 (m, 1H), 7.61 (s, 1H), 8.40 (dd, J=9.09, 6.06 Hz, 1H), 9.88 (s, 1H). LCMS (M+H)+ 347.

Workup

  1. customwas then microwaved for 1 h at 120° C
  2. customPurification
  3. washeluting with 40-80% EA in hexane over 5 min

Sources & evidence

ORD record
ord-ea347dc960eb4880b23b62743008237c
Source dataset
uspto-grants-2015_05
Patent number
US09034900B2

Reaction notes

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