Cesium carbonate → HCID 59286618, compound

HRID 1876044Notes

Reaction equation

HRID 1876044 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.[CH3:14][C:15]1[N:16]=[CH:17][N:18]([C:20]2[N:25]=[CH:24][N:23]=[C:22]([N:26]=[C:27](SC)SC)[CH:21]=2)[CH:19]=1.C(=O)([O-])[O-:33].[Cs+].[Cs+]>CN(C=O)C.C(Cl)(Cl)Cl>[CH3:5][OH:13].[NH4+:3].[OH-:33].[CH3:14][C:15]1[N:16]=[CH:17][N:18]([C:20]2[N:25]=[CH:24][N:23]=[C:22]([NH:26][C:27]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:21]=2)[CH:19]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 59286669Carbonimidodithioic acid, N-[6-(4-methyl-1H-imidazol-1-yl)-4-pyrimidinyl]-, dimethyl esterHCID 66724709(S)-3-(aminomethyl)quinuclidin-3-ol dihydrochloride

Product 2

HCID 21894508Ammonium hydroxide methanolHCID 59286618HCID 59286618, compoundYield 154.5%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6228DimethylformamideSolvent

Procedure

A suspension of (S)-3-(aminomethyl)quinuclidin-3-ol dihydrochloride (412 mg, 1.80 mmol), dimethyl 6-(4-methyl-1H-imidazol-1-yl)pyrimidin-4-ylcarbonimidodithioate (419 mg, 1.5 mmol), and cesium carbonate (1.22 g, 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 2% [95:5 MeOH/NH4OH] in CHCl3 to yield (R)—N-(6-(4-methyl-1H-imidazol-1-yl)pyrimidin-4-yl)-4H-1′-azaspiro[oxazole-5,3′-bicyclo[2.2.2]octan]-2-amine (472 mg, 92% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 9.40 (1H, br. s.), 8.56 (1H, d, J=1.01 Hz), 8.28 (1H, d, J=1.26 Hz), 7.21 (1H, s), 6.76 (1H, br. s.), 3.97 (1H, d, J=9.57 Hz), 3.63 (1H, d, J=9.57 Hz), 3.33 (1H, dd, J=14.86, 1.76 Hz), 2.62-3.05 (5H, m), 2.24 (3H, d, J=1.01 Hz), 2.03-2.19 (2H, m), 1.65-1.81 (1H, m), 1.39-1.62 (2H, m). LCMS: RT=0.25, 0.46 min, MH+=340.3.

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-6f365e2f936049439ce2b7fcf1179b2b
Source dataset
uspto-grants-2012_11
Patent number
US08309577B2

Reaction notes

Loading…