2-Amino-5-methylpyridine → HCID 66755902, compound

HRID 1177328Notes

Reaction equation

HRID 1177328 reaction equation
[Cl-].C[Al+]C.[NH2:5][C:6]1[CH:11]=[CH:10][C:9]([CH3:12])=[CH:8][N:7]=1.C([O:15][C:16]([C:18]1[CH:19]=[C:20]([O:28][C:29]2[CH:34]=[CH:33][C:32]([S:35]([CH3:38])(=[O:37])=[O:36])=[CH:31][CH:30]=2)[C:21]2[CH:25]=[C:24]([CH3:26])[S:23][C:22]=2[CH:27]=1)=O)C>ClC(Cl)C>[CH3:12][C:9]1[CH:10]=[CH:11][C:6]([NH:5][C:16]([C:18]2[CH:19]=[C:20]([O:28][C:29]3[CH:30]=[CH:31][C:32]([S:35]([CH3:38])(=[O:36])=[O:37])=[CH:33][CH:34]=3)[C:21]3[CH:25]=[C:24]([CH3:26])[S:23][C:22]=3[CH:27]=2)=[O:15])=[N:7][CH:8]=1

Participants

5

Reactant 3

HCID 153482-Amino-5-methylpyridineHCID 16686359Dimethylalumanylium chlorideHCID 66755965HCID 66755965, compound

Product 1

HCID 66755902HCID 66755902, compoundYield 68%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent2×

Procedure

Dimethylaluminum chloride (16.1 mmol, 16.1 ml of 1M in hexanes) is added to a solution of 2-amino-5-picoline (1.74 g, 16.1 mmol) in dichloroethane (10 ml) at 0 C. The mixture was allowed to warm to room temperature over a period of 1 h, then recooled to 0 C and treated with 4-(4-methanesulfonyl-phenoxy)-2-methyl-benzo[b]thiophene-6-carboxylic acid ethyl ester (0.63 g, crude product from previous step) in dichloroethane (5 ml) at 0° C. The mixture was allowed to warm to room temperature, and held at room temperature for 8 h. The reaction was quenched by the drop wise addition of MeOH (2 ml) at 0 C, followed by 1M aqueous pH6 phosphate buffer (10 ml), then ethyl acetate was added (50 ml). Separation of the organic layer followed by evaporation yields 0.80 g crude product. Purification by silica gel chromatography (0-20% MeOH—CHCl3) yielded 0.39 g (68%) of product 4-(4-methanesulfonyl-phenoxy)-2-methyl-benzo[b]thiophene-6-carboxylic acid(5-methyl-pyridin-2-yl)-amide. LRMS for C23H20N2O4S2 m/z 453 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.80 (s, 1H), 8.56 (s, 1H), 8.22 (d, J=2.3, 1H), 8.08 (d, J=8.3, 1H), 7.93 (d, J=8.8, 2H), 7.74 (d, J=1.2, 2H), 7.67 (dd, J=8.6, 2.0, 1H), 7.22 (d, J=8.8, 2H), 7.09 (s, 1H), 3.21 (s, 3H), 2.59 (d, J=1.0, 3H), 2.28 (s, 3H). Anal. Calcd. for C23H20N2O4S2: C, 61.04; H, 4.45; N, 6.19. Found: C, 61.01; H, 4.47; N, 5.96.

Workup

  1. temperatureto warm to room temperature
  2. customThe reaction was quenched by the drop wise addition of MeOH (2 ml) at 0 C
  3. additionethyl acetate was added (50 ml)
  4. customSeparation of the organic layer
  5. customfollowed by evaporation
  6. customyields 0.80 g crude product
  7. customPurification by silica gel chromatography (0-20% MeOH—CHCl3)

Sources & evidence

ORD record
ord-480b43d0e8954fd1ac38a512f8aa9fe7
Source dataset
uspto-grants-2010_11
Patent number
US07842713B2

Reaction notes

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