Cesium carbonate → HCID 58088196, compound

HRID 250139Notes

Reaction equation

HRID 250139 reaction equation
Cl.Cl.[NH2:3][CH2:4][C@@:5]1([OH:13])[CH:10]2[CH2:11][CH2:12][N:7]([CH2:8][CH2:9]2)[CH2:6]1.C([O-])([O-])=O.[Cs+].[Cs+].[Br:20][C:21]1[CH:30]=[CH:29][CH:28]=[C:27]2[C:22]=1[CH:23]=[C:24]([N:31]=[C:32]=S)[N:25]=[CH:26]2.C(N=C=NC(C)C)(C)C>CN(C)C=O>[Br:20][C:21]1[CH:30]=[CH:29][CH:28]=[C:27]2[C:22]=1[CH:23]=[C:24]([NH:31][C:32]1[O:13][C@:5]3([CH2:4][N:3]=1)[CH:10]1[CH2:9][CH2:8][N:7]([CH2:12][CH2:11]1)[CH2:6]3)[N:25]=[CH:26]2

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 12734DiisopropylcarbodiimideHCID 574766085-Bromo-3-isothiocyanatoisoquinolineHCID 66724709(S)-3-(aminomethyl)quinuclidin-3-ol dihydrochloride

Product 1

HCID 58088196HCID 58088196, compoundYield 70.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To (S)-3-(aminomethyl)quinuclidin-3-ol dihydrochloride (0.207 g, 0.905 mmol) in N,N-dimethylformamide (20 mL) was added Cs2CO3 (0.737 g, 2.263 mmol) and 5-bromo-3-isothiocyanatoisoquinoline (0.24 g, 0.905 mmol). The suspension was stirred at room temperature for 30 minutes. N,N′-Diisopropylcarbodiimide (0.423 mL, 2.72 mmol) was then added and the mixture was stirred at room temperature for 18 hours. The mixture was concentrated and purified by silica gel chromatography (5-15% [9.5:0.5 methanol:ammonium hydroxide]-ethyl acetate). The desired fractions were concentrated and further purified using 5-15% [9.5:0.5 methanol:ammonium hydroxide] in ethyl acetate to afford (R)—N-(5-bromoisoquinolin-3-yl)-4H-1′-azaspiro[oxazole-5,3′-bicyclo[2.2.2]octan]-2-amine (0.248 g, 0.634 mmol, 70% yield) as a yellow solid. 1H NMR (400 MHz, MeOD) δ ppm 8.99 (1H, s), 7.91 (2H, dd), 7.55 (1H, br. s.), 7.28 (1H, t), 3.96 (1H, d), 3.65 (1H, d), 3.17-3.26 (1H, m), 3.03-3.13 (1H, m), 2.70-2.99 (4H, m), 2.03-2.30 (2H, m), 1.47-1.87 (3H, m). LCMS:R.T.=1.69; [M+2]+=389.21.

Workup

  1. stirringthe mixture was stirred at room temperature for 18 hours
  2. concentrationThe mixture was concentrated
  3. custompurified by silica gel chromatography (5-15% [9.5:0.5 methanol:ammonium hydroxide]-ethyl acetate)
  4. concentrationThe desired fractions were concentrated
  5. customfurther purified

Sources & evidence

ORD record
ord-106b5ec5f4bf42599337b6376ba619be
Source dataset
uspto-grants-2011_01
Patent number
US07863291B2

Reaction notes

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