3-(Methylcarbamoyl)benzeneboronic acid → 3-(2'-amino-1'-methyl-5'-oxo-2-phenyl-1',5'-dihydrospiro[chroman-4,4'-imidazole]-6-yl)-N-methylbenzamide

HRID 1408647Notes

Reaction equation

HRID 1408647 reaction equation
[NH2:1][C:2]1[N:3]([CH3:24])[C:4](=[O:23])[C:5]2([C:15]3[C:10](=[CH:11][CH:12]=[C:13](Br)[CH:14]=3)[O:9][CH:8]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:7]2)[N:6]=1.[CH3:25][NH:26][C:27]([C:29]1[CH:30]=[C:31](B(O)O)[CH:32]=[CH:33][CH:34]=1)=[O:28]>O1CCOCC1.C([O-])([O-])=O.[Cs+].[Cs+].Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:1][C:2]1[N:3]([CH3:24])[C:4](=[O:23])[C:5]2([C:15]3[C:10](=[CH:11][CH:12]=[C:13]([C:33]4[CH:34]=[C:29]([CH:30]=[CH:31][CH:32]=4)[C:27]([NH:26][CH3:25])=[O:28])[CH:14]=3)[O:9][CH:8]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:7]2)[N:6]=1

Participants

6

Reactant 2

HCID 27735243-(Methylcarbamoyl)benzeneboronic acidHCID 584237682'-amino-6-bromo-1'-methyl-2-phenylspiro[chroman-4,4'-imidazol]-5'(1'H)-one

Product 1

HCID 584238263-(2'-amino-1'-methyl-5'-oxo-2-phenyl-1',5'-dihydrospiro[chroman-4,4'-imidazole]-6-yl)-N-methylbenzamideYield 4.2%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 10796Cesium carbonateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

Pd(PPh3)2Cl2 (10 mg) in a 10 mL CEM test tube under Ar was treated sequentially with 2′-amino-6-bromo-1′-methyl-2-phenylspiro[chroman-4,4′-imidazol]-5′(1′H)-one (20 mg, 0.052 mmol) in 1,4-dioxane (1 mL), Cs2CO3 (2 N, 0.3 mL) and 3-(methylcarbamoyl)phenylboronic acid (18.6 mg, 0.104 mmol). The mixture was heated in a microwave reactor at 120° C. for 30 minutes. The reaction mixture was concentrated in vacuo to give the residue, which was purified by preparative TLC and preparative HPLC to give pure 3-(2′-amino-1′-methyl-5′-oxo-2-phenyl-1′,5′-dihydrospiro[chroman-4,4′-imidazole]-6-yl)-N-methylbenzamide (0.96 mg, 4%). 1H-NMR (CDCl3): 2.36 (d, 1H), 2.57 (t, 1H), 2.73 (s, 3H), 2.97 (s, 3H), 5.87 (d, 1H), 7.11 (m, 2H), 7.45 (m, 8H), 7.51 (m, 1H), 7.60 (s, 1H), 7.78 (s, 1H).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customto give the residue, which
  3. customwas purified by preparative TLC and preparative HPLC

Sources & evidence

ORD record
ord-953ddfc2eaa442a6ac3fe94595e28608
Source dataset
uspto-grants-2014_12
Patent number
US08921359B2

Reaction notes

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