Cesium carbonate → HCID 59286606, compound

HRID 1876028Notes

Reaction equation

HRID 1876028 reaction equation
[Cl-].[NH3+:2][CH2:3][C@@:4]1([OH:12])[CH:9]2[CH2:10][CH2:11][NH+:6]([CH2:7][CH2:8]2)[CH2:5]1.[Cl-].C(=O)([O-])[O-].[Cs+].[Cs+].[N:20]([C:23]1[N:24]=[CH:25][C:26]2[C:31]([CH:32]=1)=[CH:30][C:29]([O:33][CH3:34])=[C:28]([O:35][CH3:36])[CH:27]=2)=[C:21]=S.C(=NC(C)C)=NC(C)C>CN(C=O)C.C(#N)C>[CH3:34][O:33][C:29]1[CH:30]=[C:31]2[C:26](=[CH:27][C:28]=1[O:35][CH3:36])[CH:25]=[N:24][C:23]([NH:20][C:21]1[O:12][C@:4]3([CH2:3][N:2]=1)[CH:9]1[CH2:8][CH2:7][N:6]([CH2:11][CH2:10]1)[CH2:5]3)=[CH:32]2

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 12734Diisopropylcarbodiimide2×HCID 59286644HCID 59286644, compoundHCID 178478858HCID 178478858, compound

Product 1

HCID 59286606HCID 59286606, compoundYield 20.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent3×HCID 6342AcetonitrileSolvent

Procedure

To a stirring suspension of (S)-3-(ammoniomethyl)-3-hydroxy-1-azoniabicyclo[2.2.2]octane chloride (73 mg, 0.319 mmol) and cesium carbonate (221 mg, 0.678 mmol) in DMF (5 mL) was added a solution of 3-isothiocyanato-6,7-dimethoxyisoquinoline (69 mg, 0.280 mmol) in DMF (1.5 mL) and the reaction mixture was allowed to stir at room temperature for 3 days. To the solution was then added a solution of N,N′-methanediylidenedipropan-2-amine (69 mg, 0.547 mmol) in DMF (0.4 mL) and the reaction was allowed to stand at room temperature for 14 days. Another 69 mg di-isopropylcarbodiimide was added in −0.4 mL acetonitrile and the reaction was allowed to stand for 1 more day, then it was evaporated in vacuo and the residue subjected to preparative HPLC to yield (R)—N-(6,7-dimethoxyisoquinolin-3-yl)-4H-1′-azaspiro[oxazole-5,3′-bicyclo[2.2.2]octan]-2-amine 20.9 mg. (8%) LCMS RT 0.98 min, MH+=403.2 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 8.73 (1H, s), 7.28 (1H, s), 7.09 (1H, s), 6.96 (1H, s), 4.01 (3H, s), 4.00 (3H, s), 3.96 (1H, d, J=8.5 Hz), 3.63 (1H, d, J=9.2 Hz), 3.39 (1H, d, J=15.0 Hz), 2.79-3.10 (5H, m), 2.24 (1H, br. s.), 2.15 (1H, br. s.), 1.75 (1H, dddd, J=13.9, 9.3, 4.7, 4.4 Hz), 1.59-1.68 (1H, m), 1.48-1.59 (1H, m)

Workup

  1. waitto stand at room temperature for 14 days
  2. customit was evaporated in vacuo

Sources & evidence

ORD record
ord-73b70667485a4ffb91fbf865f2c63181
Source dataset
uspto-grants-2012_11
Patent number
US08309577B2

Reaction notes

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