Triethylamine → 4-(5-m-TOLYL-BENZOOXAZOL-2-YL)-1,4-DIAZA-BICYCLO[3.2.2]NONANE

HRID 393542Notes

Reaction equation

HRID 393542 reaction equation
CCN(CC)CC.Br[C:9]1[CH:10]=[CH:11][C:12]2[O:16][C:15]([N:17]3[CH:23]4[CH2:24][CH2:25][N:20]([CH2:21][CH2:22]4)[CH2:19][CH2:18]3)=[N:14][C:13]=2[CH:26]=1.[C:27]1([CH3:36])[CH:32]=[CH:31][CH:30]=[C:29](B(O)O)[CH:28]=1.[F-].[Cs+]>COCCOC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN(C1C=CC=CC=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1)C>[C:27]1([CH3:36])[CH:32]=[CH:31][CH:30]=[C:29]([C:9]2[CH:10]=[CH:11][C:12]3[O:16][C:15]([N:17]4[CH:23]5[CH2:24][CH2:25][N:20]([CH2:21][CH2:22]5)[CH2:19][CH2:18]4)=[N:14][C:13]=3[CH:26]=2)[CH:28]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 25953Cesium fluorideHCID 27339503-Tolylboronic acidHCID 224957824-(5-Bromobenzoxazol-2-yl)-1,4-diazabicyclo[3.2.2]nonane

Product 1

HCID 224958114-(5-m-TOLYL-BENZOOXAZOL-2-YL)-1,4-DIAZA-BICYCLO[3.2.2]NONANEYield 75.5%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

Et3N (5 μL) was added to a solution of palladium (II) acetate (0.7 mg, 3.1 μmol) and 2-(N,N-dimethylamino)-2′-dicyclohexylphosphinobiphenyl (1.8 mg, 4.65 μmol) in 1,2-dimethoxyethane (0.5 mL) under a nitrogen atmosphere at RT. 4-(5-Bromo-benzooxazol-2-yl)-1,4-diaza-bicyclo[3.2.2]nonane (50 mg, 0.155 mmol, prepared in example 9), m-tolylboronic acid (32 mg, 0.233 mmol) and CsF (70 mg, 0.465 mmol) were added to the solution and the mixture was heated in an oil bath (temp=80° C.) for a period of 16 h. The reaction mixture was cooled to RT, filtered through a pad of celite and concentrated in vacuo. The crude residue was purified by chromatography (Biotage, 12L) eluting with 4% MeOH in CHCl3 with 1 mL of NH4OH per L to give 39 mg (75%) of the title compound as a film: 1H NMR (CDCl3, 400 MHz) δ 7.55 (d, 1H, J=1.7 Hz), 7.40-7.38 (m, 2H), 7.33-7.26 (m, 2H), 7.22-7.19 (m, 1H), 7.14 (d, 1H, J=7.4 Hz), 4.54-4.52 (m, 1H), 3.94 (t, 2H, J=5.8 Hz), 3.19-3.12 (m, 4H), 3.06-2.99 (m, 2H), 2.41 (s, 3H), 2.20-2.13 (m, 2H), 1.86-1.78 (m, 2H); 13C NMR (CDCl3, 100 MHz) δ 162.2, 148.6, 144.3, 141.9, 138.5, 138.0, 128.9, 128.4, 127.8, 124.6, 119.8, 114.8, 108.7, 57.3, 50.4, 46.5, 44.4, 27.0, 21.8; MS (Cl) m/z 334,1 (M+1).

Workup

  1. temperatureThe reaction mixture was cooled to RT
  2. filtrationfiltered through a pad of celite
  3. concentrationconcentrated in vacuo
  4. customThe crude residue was purified by chromatography (Biotage, 12L)
  5. washeluting with 4% MeOH in CHCl3 with 1 mL of NH4OH per L

Sources & evidence

ORD record
ord-a9440299597042aab4dd8c1b8c571b96
Source dataset
uspto-grants-2004_10
Patent number
US06809094B2

Reaction notes

Loading…