Cesium carbonate → HCID 59286641, compound

HRID 1876053Notes

Reaction equation

HRID 1876053 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.[N:14]1([C:19]2[N:24]=[CH:23][N:22]=[C:21]([N:25]=[C:26](SC)SC)[CH:20]=2)[CH:18]=[N:17][CH:16]=[N:15]1.C(=O)([O-])[O-:32].[Cs+].[Cs+]>CN(C=O)C.C(Cl)(Cl)Cl>[CH3:5][OH:13].[NH4+:3].[OH-:32].[N:14]1([C:19]2[N:24]=[CH:23][N:22]=[C:21]([NH:25][C:26]3[O:13][C@:5]4([CH2:4][N:3]=3)[CH:10]3[CH2:9][CH2:8][N:7]([CH2:12][CH2:11]3)[CH2:6]4)[CH:20]=2)[CH:18]=[N:17][CH:16]=[N:15]1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 59286684Carbonimidodithioic acid, N-[6-(1H-1,2,4-triazol-1-yl)-4-pyrimidinyl]-, dimethyl esterHCID 66724709(S)-3-(aminomethyl)quinuclidin-3-ol dihydrochloride

Product 2

HCID 21894508Ammonium hydroxide methanolHCID 59286641HCID 59286641, compoundYield 71.5%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6228DimethylformamideSolvent

Procedure

A suspension of (S)-3-(aminomethyl)quinuclidin-3-ol dihydrochloride (412 mg, 1.800 mmol), dimethyl 6-(1H-1,2,4-triazol-1-yl)pyrimidin-4-ylcarbonimidodithioate (400 mg, 1.5 mmol), and cesium carbonate (1222 mg, 3.75 mmol) was stirred in DMF (3.8 mL) at 75° C. for 2 h. The reaction was concentrated and purified by flash chromatography on a 40 g silica gel cartridge with a pre-run of 1% [95:5 MeOH/NH4OH] in EtOAc, then 1 to 3% [95:5 MeOH/NH4OH] in CHCl3 to yield (R)—N-(6-(1H-1,2,4-triazol-1-yl)pyrimidin-4-yl)-4H-1′-azaspiro[oxazole-5,3′-bicyclo[2.2.2]octan]-2-amine (210 mg, 43% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 9.45 (1H, br. s.), 9.14 (1H, s), 8.61 (1H, d, J=1.01 Hz), 8.08 (1H, s), 7.39 (1H, s), 4.00 (1H, d, J=9.57 Hz), 3.67 (1H, d, J=9.57 Hz), 3.38 (1H, dd, J=14.86, 1.76 Hz), 2.71-3.08 (5H, m), 2.08-2.23 (2H, m), 1.68-1.80 (1H, m), 1.45-1.64 (2H, m). LCMS: RT=0.46 min, MH+=327.2

Workup

  1. concentrationThe reaction was concentrated
  2. custompurified by flash chromatography on a 40 g silica gel cartridge with a pre-run of 1% [95:5 MeOH/NH4OH] in EtOAc

Sources & evidence

ORD record
ord-ebeddcdfc37b4710963635140d0f4070
Source dataset
uspto-grants-2012_11
Patent number
US08309577B2

Reaction notes

Loading…