Pyridine → HCID 178432776, compound

HRID 75518Notes

Reaction equation

HRID 75518 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][C:5]([CH3:19])=[C:6]([CH:18]=1)[C:7]([NH:9][C@H:10]1[CH2:15][CH2:14][C@H:13]([CH2:16][OH:17])[CH2:12][CH2:11]1)=[O:8].N1C=CC=CC=1.[CH3:26][S:27](Cl)(=[O:29])=[O:28]>C(Cl)Cl>[Cl:1][C:2]1[CH:18]=[C:6]([C:7]([NH:9][C@H:10]2[CH2:11][CH2:12][C@H:13]([CH2:16][O:17][S:27]([CH3:26])(=[O:29])=[O:28])[CH2:14][CH2:15]2)=[O:8])[C:5]([CH3:19])=[N:4][CH:3]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 31297Methanesulfonyl chlorideHCID 178432775HCID 178432775, compound2×

Product 1

HCID 178432776HCID 178432776, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of trans-5-chloro-N-(4-hydroxymethyl-cyclohexyl)-2-methyl-nicotinamide (Intermediate E, step 2) (100 mg, 0.354 mmol) and pyridine (3.6 ml) in dry DCM (3.5 ml) under nitrogen was cooled to approx. 0° C. using an ice-water bath. Methanesulfonyl chloride (0.030 ml, 0.389 mmol) was added dropwise. The reaction mixture was allowed to warm to room temp and stirred at this temp for 4 hours. The reaction was quenched by the addition of sat. NH4Cl at room temp and then extracted with diethyl ether (3×20 ml). The Et2O extracts were combined, washed with sat brine (20 ml), dried (MgSO4), filtered and evaporated to give the title compound as a colourless solid. LCMS 361.2/363.2 [M+H]+. 1H NMR (400 MHz, CDCl3) δ 8.52 (1H, d), 7.65 (1H, d), 5.68 (1H, br d), 4.09 (2H, d), 3.96 (1H, m), 3.04 (3H, s), 2.65 (3H, s), 2.21 (2H, m), 1.96 (2H, m), 1.79 (1H, m), 1.27 (4H, m).

Workup

  1. customThe reaction was quenched by the addition of sat. NH4Cl at room temp
  2. extractionextracted with diethyl ether (3×20 ml)
  3. washwashed with sat brine (20 ml)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customevaporated

Sources & evidence

ORD record
ord-4619c82e3ed14832bff794aca1f8f740
Source dataset
uspto-grants-2014_09
Patent number
US08835444B2

Reaction notes

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