Cesium carbonate → HCID 67175880, compound

HRID 2096424Notes

Reaction equation

HRID 2096424 reaction equation
[NH2:1][C:2]1[N:3]([CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[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.C([O-])([O-])=O.[Cs+].[Cs+].[C:37]([C:39]1[CH:40]=[C:41](B(O)O)[CH:42]=[CH:43][CH:44]=1)#[N:38]>O1CCOCC1>[NH2:1][C:2]1[N:3]([CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:4](=[O:23])[C@@:5]2([C:15]3[C:10](=[CH:11][CH:12]=[C:13]([C:43]4[CH:44]=[C:39]([CH:40]=[CH:41][CH:42]=4)[C:37]#[N:38])[CH:14]=3)[O:9][C@@H:8]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:7]2)[N:6]=1.[NH2:1][C:2]1[N:3]([CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:4](=[O:23])[C@@:5]2([C:15]3[C:10](=[CH:11][CH:12]=[C:13]([C:43]4[CH:44]=[C:39]([CH:40]=[CH:41][CH:42]=4)[C:37]#[N:38])[CH:14]=3)[O:9][C@H:8]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:7]2)[N:6]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 27343253-Cyanophenylboronic acidHCID 58424030HCID 58424030, compound

Product 2

HCID 58424043HCID 58424043, compoundYield 4.8%HCID 67175880HCID 67175880, compoundYield 33%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
130 °C

Procedure

To a solution of 2′-amino-1′-benzyl-6-bromo-2-phenylspiro[chroman-4,4′-imidazol]-5′(1′H)-one (17.3 mg, 0.04 mmol) in 1,4-dioxane (1.5 mL) was added Cs2CO3 (excess), 3-cyanophenylboronic acid (excess), and catalytical amount of PdCl2dppf. After degassing, the resulting mixture was heated in a CEM microwave reactor at 130° C. for 30 min. Solvent was removed in vacuo and the residue was purified by reverse phase HPLC to give 3-((2R,4R)-2′-amino-1′-benzyl-5′-oxo-2-phenyl-1′,5′-dihydrospiro[chroman-4,4′-imidazole]-6-yl)benzonitrile (6.0 mg, 33%) as a TFA salt (25b) and 3-((2S,4R)-2′-amino-1′-benzyl-5′-oxo-2-phenyl-1′,5′-dihydrospiro[chroman-4,4′-imidazole]-6-yl)benzonitrile (0.86 mg, 4.8%) as a TFA salt. (25a). 1H NMR (400 MHz, CD3OD): 7.84-7.60 (m, 4 H), 7.74-7.24 (m, 12 H), 7.12 (d, 1 H), 5.92 (d, 1 H), 4.62 (s, 2 H), 2.60 (d, 1 H), 2.42 (d, 1 H); MS m/z 485 (M+H+) (25b). 1H NMR (400 MHz, CD3OD): 7.74-7.36 (m, 16 H), 7.16 (d, 1 H), 5.24 (d, 1 H), 5.08, 5.00 (two d, 2 H), 2.64 (d, 1 H), 2.56 (d, 1 H); MS m/z 485 (M+H+) (25a).

Workup

  1. customAfter degassing
  2. customSolvent was removed in vacuo
  3. customthe residue was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-a93349ec4d654be99b5fccc519dfef32
Source dataset
uspto-grants-2013_05
Patent number
US08450308B2

Reaction notes

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