2,4,6-Trimethylpyridine → HCID 10296090, compound

HRID 1168191Notes

Reaction equation

HRID 1168191 reaction equation
[Cl:1][C:2]1[CH:25]=[CH:24][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:19](=[O:20])[C:18]3[C:13](=[CH:14][CH:15]=[C:16]([CH2:21]O)[CH:17]=3)[N:12]([CH3:23])[N:11]=2)=[O:9])=[CH:4][CH:3]=1.N1C(C)=CC(C)=CC=1C.CS(Cl)(=O)=O.[NH:40]1[CH2:45][CH2:44][O:43][CH2:42][CH2:41]1>CN(C1C=CN=CC=1)C.CN(C=O)C.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:19](=[O:20])[C:18]3[C:13](=[CH:14][CH:15]=[C:16]([CH2:21][N:40]4[CH2:45][CH2:44][O:43][CH2:42][CH2:41]4)[CH:17]=3)[N:12]([CH3:23])[N:11]=2)=[O:9])=[CH:24][CH:25]=1

Participants

8

Reactant 4

HCID 79532,4,6-TrimethylpyridineHCID 8083MorpholineHCID 31297Methanesulfonyl chlorideHCID 10269737HCID 10269737, compound

Product 1

HCID 10296090HCID 10296090, compoundYield 46%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of N-(4-chlorobenzyl)-6-(hydroxymethyl)-1-methyl-4-oxo-1,4-dihydro-3-cinnolinecarboxamide [Example 4] (0.062 g), DMAP (0.015 g) and collidine (0.030 mL) in 5 mL anhydrous DMF in a flame-dried flask is added methanesulfonyl chloride (0.015 mL) in one portion. The reaction is stirred at room temperature for 18 h. Morpholine (0.16 mL) is then added in one portion and the reaction is stirred at room temperature for 5 h. The reaction is poured into 50 mL water. The aqueous solution is extracted 3× with CH2Cl2, then 2× with EtOAc. The organics are combined, dried over Na2SO4, filtered and concentrated. The residue is dissolved in CH2Cl2 and adsorbed onto silica. Purification by Biotage Flash 40S (eluent CH2Cl2 (1L), 1% MeOH/CH2Cl2 (1L), 2% MeOH/CH2Cl2 (1L), 3.5% MeOH/CH2Cl2 (1L), 5% MeOH/CH2Cl2 (1L)) affords the desired product as a pale yellow solid (0.034 g, 46%). Physical characteristics are as follows: m.p. 190-192° C.; 1H NMR (300 MHz, DMSO-d6) δ8.17, 7.94, 7.40, 4.56, 4.26, 3.66, 3.58, 2.39; MS (ESI) m/z 427.0 (M+H)+; HRMS (FAB) calcd for C22H23ClN4O3+H1 427.1537, found 427.1544. An alternate synthesis route for Example 5 is as follows:

Workup

  1. stirringthe reaction is stirred at room temperature for 5 h
  2. extractionThe aqueous solution is extracted 3× with CH2Cl2
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. dissolutionThe residue is dissolved in CH2Cl2
  7. customPurification by Biotage Flash 40S (eluent CH2Cl2 (1L), 1% MeOH/CH2Cl2 (1L), 2% MeOH/CH2Cl2 (1L), 3.5% MeOH/CH2Cl2 (1L), 5% MeOH/CH2Cl2 (1L))

Sources & evidence

ORD record
ord-601f080bb1a247f792525fa31a36a58d
Source dataset
uspto-grants-2003_09
Patent number
US06624160B2

Reaction notes

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