Dimethylformamide → HCID 58088120, compound

HRID 250098Notes

Reaction equation

HRID 250098 reaction equation
Cl.Cl.[NH2:3][CH2:4][C@@:5]1(O)[CH:10]2[CH2:11][CH2:12][N:7]([CH2:8][CH2:9]2)[CH2:6]1.[C:14]([O-])([O-])=O.[Cs+].[Cs+].ClC1N=C[N:24]=[C:23]([N:27]=[C:28](SC)[S:29][CH3:30])C=1.C[N:34]([CH3:37])[CH:35]=[O:36]>>[CH3:30][S:29][C:28]1[N:27]=[CH:23][N:24]=[C:37]([NH:34][C:35]2[O:36][C@:5]3([CH2:4][N:3]=2)[CH:10]2[CH2:11][CH2:12][N:7]([CH2:8][CH2:9]2)[CH2:6]3)[CH:14]=1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 58088051HCID 58088051, compoundHCID 66724709(S)-3-(aminomethyl)quinuclidin-3-ol dihydrochloride

Product 1

HCID 58088120HCID 58088120, compoundYield 48.2%

Procedure

To (S)-3-(aminomethyl)quinuclidin-3-ol dihydrochloride (0.9 g, 3.93 mmol) in N,N-dimethylformamide (20 mL) was added Cs2CO3 (2.69 g, 8.25 mmol) and dimethyl 6-chloropyrimidin-4-ylcarbonimidodithioate (0.964 g, 4.12 mmol). The suspension was stirred at room temperature for 18 hours, then heated at 100 C for 3 hours. The mixture was concentrated and purified by silica gel chromatography (5-15% 9:1 methanol:ammonium hydroxide-ethyl acetate) to afford (R)—N-(6-(methylthio)pyrimidin-4-yl)-4H-1′-azaspiro[oxazole-5,3′-bicyclo[2.2.2]octan]-2-amine (0.21 g, 0.72 mmol, 48.2% yield) as a pale yellow solid. 1H NMR (400 MHz, CDCl3) δ ppm 9.43 (1 H, br. s.), 8.55 (1 H, d), 6.78 (1 H, br. s.), 3.98 (1 H, d), 3.64 (1 H, d), 3.37 (1 H, dd), 2.72-3.06 (5 H, m), 2.51 (3 H, s), 2.08-2.24 (2 H, m), 1.69-1.81 (1 H, m), 1.41-1.64 (2 H, m). LCMS R.T.=0.93; [M+H]+=306.29.

Workup

  1. temperatureheated at 100 C for 3 hours
  2. concentrationThe mixture was concentrated
  3. custompurified by silica gel chromatography (5-15% 9:1 methanol:ammonium hydroxide-ethyl acetate)

Sources & evidence

ORD record
ord-91abf361828c4c56bba4ec922f512f8e
Source dataset
uspto-grants-2011_01
Patent number
US07863291B2

Reaction notes

Loading…