4-Cyanophenylboronic acid → HCID 58424685, compound

HRID 1408577Notes

Reaction equation

HRID 1408577 reaction equation
[NH2:1][C:2]1[N:3]([CH3:23])[C:4](=[O:22])[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[S:18][CH:19]=[CH:20][CH:21]=3)[CH2:7]2)[N:6]=1.[C:24]([C:26]1[CH:31]=[CH:30][C:29](B(O)O)=[CH:28][CH:27]=1)#[N:25]>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]([CH3:23])[C:4](=[O:22])[C@:5]2([C:15]3[C:10](=[CH:11][CH:12]=[C:13]([C:28]4[CH:27]=[C:26]([CH:31]=[CH:30][CH:29]=4)[C:24]#[N:25])[CH:14]=3)[O:9][C@H:8]([C:17]3[S:18][CH:19]=[CH:20][CH:21]=3)[CH2:7]2)[N:6]=1.[NH2:1][C:2]1[N:3]([CH3:23])[C:4](=[O:22])[C@:5]2([C:15]3[C:10](=[CH:11][CH:12]=[C:13]([C:28]4[CH:27]=[C:26]([CH:31]=[CH:30][CH:29]=4)[C:24]#[N:25])[CH:14]=3)[O:9][C@@H:8]([C:17]3[S:18][CH:19]=[CH:20][CH:21]=3)[CH2:7]2)[N:6]=1

Participants

7

Reactant 2

HCID 27343264-Cyanophenylboronic acidHCID 58423951HCID 58423951, compound

Product 2

HCID 58424685HCID 58424685, compoundYield 1%HCID 58424787HCID 58424787, compoundYield 1%

Reagents, catalysts & solvents 3

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

Procedure

Pd(PPh3)2Cl2 (20 mg) in a 10 mL of flask under Ar was treated sequentially with 2′-amino-6-bromo-1′-methyl-2-(thiophen-2-yl)spiro[chroman-4,4′-imidazol]-5′(1′H)-one (46 mg, 0.117 mmol) in 1,4-dioxane (5 mL), Cs2CO3 (2 N, 0.5 mL) and 4-cyanophenylboronic acid (34.5 mg, 0.23 mmol). The mixture was refluxed under Ar for 2 h. The reaction mixture was concentrated in vacuo to give the residue, which was purified by preparative TLC followed by preparative HPLC to give pure 3-((2S,4S)-2′-amino-1′-methyl-5′-oxo-2-(thiophen-2-yl)-1′,5′-dihydrospiro[chroman-4,4′-imidazole]-6-yl)benzonitrile (Compound 8a, 1.35 mg, 1%), 1H-NMR (CDCl3): 442-069-3B: 2.30 (d, 1H), 2.49 (d, 1H), 3.01 (d, 3H), 5.81 (dd, 1H), 6.95 (t, 1H), 7.00 (m, 2H), 7.05 (s, 1H), 7.30 (d, 1H), 7.40 (d, 1H), 7.49 (d, 1H), 7.51 (t, 1H), 7.61 (t, 2H), and 3-((2R,4S)-2′-Amino-1′-methyl-5′-oxo-2-(thiophen-2-yl)-1′,5′-dihydrospiro[chroman-4,4′-imidazole]-6-yl)-benzonitrile (Compound 8b, 1.10 mg, 1%). 1H-NMR (CDCl3): 2.40 (d, 1H), 2.63 (t, 1H), 3.31 (s, 3H), 6.12 (d, 1H), 6.95 (t, 1H), 7.00 (d, 1H), 7.05 (m, 2H), 7.30 (d, 1H), 7.48 (m, 2H), 7.54 (d, 1H), 7.68 (t, 2H).

Workup

  1. temperatureThe mixture was refluxed under Ar for 2 h
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. customto give the residue, which
  4. customwas purified by preparative TLC

Sources & evidence

ORD record
ord-46ce69510504466492f9dcc886c0740a
Source dataset
uspto-grants-2014_12
Patent number
US08921359B2

Reaction notes

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