Pyridine → HCID 58739063, compound

HRID 720287Notes

Reaction equation

HRID 720287 reaction equation
[CH2:1]([O:8][C:9]1[C:14](=[O:15])[N:13]([CH3:16])[C:12]([N:17]2[CH2:22][CH2:21][CH2:20][CH2:19][S:18]2(=[O:24])=[O:23])=[N:11][C:10]=1[C:25]([OH:27])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl-].ClC=[N+](C)C.[F:34][C:35]1[CH:41]=[CH:40][C:38]([NH2:39])=[CH:37][CH:36]=1.N1C=CC=CC=1>ClCCl>[F:34][C:35]1[CH:41]=[CH:40][C:38]([NH:39][C:25]([C:10]2[N:11]=[C:12]([N:17]3[CH2:22][CH2:21][CH2:20][CH2:19][S:18]3(=[O:24])=[O:23])[N:13]([CH3:16])[C:14](=[O:15])[C:9]=2[O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[O:27])=[CH:37][CH:36]=1

Participants

6

Reactant 4

HCID 1049PyridineHCID 97314-FluoroanilineHCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 58739082HCID 58739082, compound

Product 1

HCID 58739063HCID 58739063, compoundYield 108.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 5-benzyloxy-2-(1,1-dioxo-1λ6-[1,2]thiazinan-2-yl)-1-methyl-6-oxo-1,6-dihydro-pyrimidine-4-carboxylic acid (0.200 g, 0.51 mmol) in dichloromethane (20 ml) was treated at 25° C. with (chloromethylene)dimethylammonium chloride (0.080 g, 0.62 mmol) and the resulting mixture was stirred for 15 min. Then a solution of 4-fluoroaniline (0.117 g, 1.06 mmol) and pyridine (0.1 ml, 1.2 mmol) in dichloromethane (2 ml) was added and the reaction mixture was stirred for another 45 min. The mixture was quenched by addition of ethyl acetate and pH 6 phosphate buffer. The organic phase was then washed with saturated sodium bicarbonate, brine and dried over anhydrous magnesium sulfate. Evaporation of the solvent and chromatography of the residue on silica gel (elution toluene-ethyl acetate 7:3) gave 0.270 g (88% yield) of the title amide as white crystals; mp 201–202° C.(ethyl acetate). 1HNMR 400 MHz (CDCl3) δ (ppm): 1.65–1.69 and 2.35–2.7 (1H and 3H, 2 m, 2×CH2), 3.2–3.25 (1H, m, CH), 3.59–3.73 (2H, m, CH2), 3.68 (3H, s, NCH3), 3.99–4.07 (1H, m, CH), 5.47 (2H, AB system, JAB=10.8 Hz, Δν=49.8 Hz, OCH2), 6.93 (2H, m, aromatics), 7.22 (2H, m, aromatics), 7.39–7.52 (5H, m, aromatics) Anal. Calcd for C23H23FN4O5S: C, 56.78; H, 4.77; N, 11.52. Found: C, 56.83; H, 4.58; N, 11.53.

Workup

  1. stirringthe reaction mixture was stirred for another 45 min
  2. customThe mixture was quenched by addition of ethyl acetate and pH 6 phosphate buffer
  3. washThe organic phase was then washed with saturated sodium bicarbonate, brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customEvaporation of the solvent and chromatography of the residue on silica gel (elution toluene-ethyl acetate 7:3)

Sources & evidence

ORD record
ord-630ef5f2d5cf48758e5b56e55e3862e5
Source dataset
uspto-grants-2006_11
Patent number
US07135467B2

Reaction notes

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