Cesium carbonate → 2'-methyl-2-phenyl-6-(pyridin-3-yl)-2'H-spiro[chroman-4,5'-[1,2,4]oxadiazol]-3'-amine

HRID 2096568Notes

Reaction equation

HRID 2096568 reaction equation
OC(C(F)(F)F)=O.Br[C:9]1[CH:10]=[C:11]2[C:18]3([O:22][N:21]([CH3:23])[C:20]([NH2:24])=[N:19]3)[CH2:17][CH:16]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[O:15][C:12]2=[CH:13][CH:14]=1.[N:31]1[CH:36]=[CH:35][CH:34]=[C:33](B(O)O)[CH:32]=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.O.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>[CH3:23][N:21]1[C:20]([NH2:24])=[N:19][C:18]2([C:11]3[C:12](=[CH:13][CH:14]=[C:9]([C:33]4[CH:32]=[N:31][CH:36]=[CH:35][CH:34]=4)[CH:10]=3)[O:15][CH:16]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH2:17]2)[O:22]1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 27343783-Pyridinylboronic acidHCID 866574456-bromo-2'-methyl-2-phenylspiro[chroman-4,5'-[1,2,4]oxadiazolidin]-3'-imine TFA salt

Product 1

HCID 584241312'-methyl-2-phenyl-6-(pyridin-3-yl)-2'H-spiro[chroman-4,5'-[1,2,4]oxadiazol]-3'-amineYield 35.1%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 6-bromo-2′-methyl-2-phenyl-2′H-spiro[chroman-4,5′-[1,2,4]oxadiazol]-3′-amine TFA salt (65 mg, 0.13 mmol), 3-pyridineboronic acid (64 mg, 0.52 mmol) and Cs2CO3 (127 mg, 0.39 mmol) in 1,4-dioxane (3 mL) and H2O (0.5 mL) in a 10 mL CEM microwave test tube was added PdCl2(PPh3)2 (10 mg). After degassing by purging with N2, the mixture was heated to 100° C. for 5 min in a CEM microwave reactor. The solvent was removed under reduced pressure and the residue was purified by preparative HPLC to give 2′-methyl-2-phenyl-6-(pyridin-3-yl)-2′H-spiro[chroman-4,5′-[1,2,4]oxadiazol]-3′-amine (17 mg) as a TFA salt. MS ESI +ve m/z 393 (M+H)+. 1H-NMR (400 MHz, CD3OD): 9.19 (br s, 1H), 8.87 (d, J=7.6 Hz, 1H), 8.78 (br s, 1H), 8.23 (d, J=2.4 Hz, 1H), 8.11 (t, J=6.4 Hz, 1H), 7.91 (dd, J=8.8, 2.4 Hz, 1H), 7.54-7.38 (m, 5H), 7.21 (d, J=8.8 Hz, 1H), 5.37 (d, 12.8 Hz, 1H), 3.43 (s, 3H), 2.88 (dd, J=14.4, 2.0 Hz, 1H), 2.42 (dd, J=14.4, 12.8 Hz, 1H).

Workup

  1. customAfter degassing
  2. customby purging with N2
  3. customThe solvent was removed under reduced pressure
  4. customthe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-38597af5e65742bcb15bff56fa6a459a
Source dataset
uspto-grants-2013_05
Patent number
US08450308B2

Reaction notes

Loading…