4-Toluenesulfonyl chloride → HCID 57410025, compound

HRID 2046226Notes

Reaction equation

HRID 2046226 reaction equation
C1(C)C=CC(S([Cl:10])(=O)=O)=CC=1.O[CH2:13][C:14]1[N:19]=[C:18]([N:20]2[CH2:25][CH2:24][N:23]3[N:26]=[C:27]([CH2:29][O:30][C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)[CH:28]=[C:22]3[C:21]2=[O:37])[CH:17]=[CH:16][CH:15]=1.C([O-])(O)=O.[Na+]>C(Cl)Cl>[Cl:10][CH2:13][C:14]1[N:19]=[C:18]([N:20]2[CH2:25][CH2:24][N:23]3[N:26]=[C:27]([CH2:29][O:30][C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)[CH:28]=[C:22]3[C:21]2=[O:37])[CH:17]=[CH:16][CH:15]=1

Participants

5

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 516892Sodium BicarbonateHCID 67974018HCID 67974018, compound

Product 1

HCID 57410025HCID 57410025, compoundYield 27.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

Toluene-4-sulfonyl chloride (73 mg, 0.38 mmol) was added to a solution of 5-(6-hydroxymethyl-pyridin-2-yl)-2-phenoxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one (67 mg, 0.19 mmol) and TEA (0.06 mL, 0.478 mmol) in DCM (1 mL) at 0° C. The reaction was stirred for 10 minutes at 100° C. under microwave irradiation. The mixture was basified with a saturated solution of NaHCO3, the organic layer was separated, dried (Na2SO4) and the solvent evaporated in vacuo. The residue was purified by flash column chromatography (silica, AcOEt in DCM 0/100 to 10/90). Desired fractions were collected and the solvent evaporated in vacuo. The residue was triturated with DIPE to yield 5-(6-chloromethyl-pyridin-2-yl)-2-phenoxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one (19 mg, 27% yield) as an off-white solid. 1H NMR (400 MHz, CDCl3) δ ppm 4.47-4.56 (m, 2H), 4.62 (s, 2H), 4.62-4.67 (m, 2H), 5.13 (s, 2H), 6.94-7.00 (m, 1H), 7.00-7.05 (m, 2H), 7.08 (s, 1H), 7.27-7.35 (m, 3H), 7.77 (dd, J=8.3, 7.6 Hz, 1H), 8.02 (d, J=8.3 Hz, 1H).

Workup

  1. customthe organic layer was separated
  2. dry with materialdried (Na2SO4)
  3. customthe solvent evaporated in vacuo
  4. customThe residue was purified by flash column chromatography (silica, AcOEt in DCM 0/100 to 10/90)
  5. customDesired fractions were collected
  6. customthe solvent evaporated in vacuo
  7. customThe residue was triturated with DIPE

Sources & evidence

ORD record
ord-5b1291755e114bcfa7f83bc4731bb009
Source dataset
uspto-grants-2013_11
Patent number
US08592422B2

Reaction notes

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