Water → HCID 58088130, compound

HRID 1875978Notes

Reaction equation

HRID 1875978 reaction equation
[CH3:1][O:2][C:3]1[C:4]2[N:12]=[C:11]([N:13]=[C:14](SC)SC)[S:10][C:5]=2[N:6]=[C:7]([CH3:9])[N:8]=1.Cl.Cl.[NH2:21][CH2:22][C@@:23]1([OH:31])[CH:28]2[CH2:29][CH2:30][N:25]([CH2:26][CH2:27]2)[CH2:24]1.C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C=O)C>[CH3:1][O:2][C:3]1[C:4]2[N:12]=[C:11]([NH:13][C:14]3[O:31][C@:23]4([CH2:22][N:21]=3)[CH:28]3[CH2:29][CH2:30][N:25]([CH2:26][CH2:27]3)[CH2:24]4)[S:10][C:5]=2[N:6]=[C:7]([CH3:9])[N:8]=1

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 58088110HCID 58088110, compoundHCID 66724709(S)-3-(aminomethyl)quinuclidin-3-ol dihydrochloride

Product 1

HCID 58088130HCID 58088130, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of dimethyl 7-methoxy-5-methylthiazolo[5,4-d]pyrimidin-2-ylcarbonimidodithioate (56 mg, 0.19 mmol), (S)-3-(aminomethyl)quinuclidin-3-ol dihydrochloride (51 mg, 0.22 mmol) and cesium carbonate (175 mg, 0.54 mmol) in DMF (0.5 mL) was heated to 100° C. for 2 hours. The reaction mixture was cooled to ambient temperature, poured into water and extracted with chloroform (4×). The combined organics were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The mixture was purified by silica gel chromatography (2-40% [9:1 methanol:ammonium hydroxide]-chloroform). The product fractions were combined and concentrated in vacuo to afford (R)—N-(7-methoxy-5-methylthiazolo[5,4-d]pyrimidin-2-yl)-4H-1′-azaspiro[oxazole-5,3′-bicyclo[2.2.2]octan]-2-amine (34 mg, 50% yield). 1H NMR (400 MHz, CDCl3) δ ppm 9.10 (br. s., 1H) 4.14 (s, 3H) 4.03 (d, J=9.54 Hz, 1H) 3.68 (d, J=9.54 Hz, 1H) 3.39 (dd, J=14.93, 1.63 Hz, 1H) 2.74-3.07 (m, 5H) 2.68 (s, 3H) 2.04-2.28 (m, 2H) 1.70-1.86 (m, 1H) 1.44-1.67 (m, 2H). MS (LC/MS) R.T.=1.10; [M+H]+=361.32.

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. extractionextracted with chloroform (4×)
  3. washThe combined organics were washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe mixture was purified by silica gel chromatography (2-40% [9:1 methanol:ammonium hydroxide]-chloroform)
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d5dfed13683a4eb9831bafb8783d4cfb
Source dataset
uspto-grants-2012_11
Patent number
US08309577B2

Reaction notes

Loading…