2-Amino-5-methylpyridine → HCID 66755653, compound

HRID 1643793Notes

Reaction equation

HRID 1643793 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:27][C:28]2[CH:33]=[CH:32][C:31]([S:34]([CH3:37])(=[O:36])=[O:35])=[CH:30][CH:29]=2)[C:21]2[CH:25]=[CH:24][S:23][C:22]=2[CH:26]=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:27][C:28]3[CH:29]=[CH:30][C:31]([S:34]([CH3:37])(=[O:36])=[O:35])=[CH:32][CH:33]=3)[C:21]3[CH:25]=[CH:24][S:23][C:22]=3[CH:26]=2)=[O:15])=[N:7][CH:8]=1

Participants

5

Reactant 3

HCID 153482-Amino-5-methylpyridineHCID 16686359Dimethylalumanylium chlorideHCID 66755700HCID 66755700, compound

Product 1

HCID 66755653HCID 66755653, compoundYield 59%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent2×

Procedure

Dimethylaluminum chloride (15.5 mmol, 15.5 ml of 1M in hexanes) was added to a solution of 2-amino-5-picoline (1.67g, 15.5 mmol) in dichloroethane (10 ml) at 0 C. The mixture was allowed to warm to room temperature, held 30 minutes at room temperature, then recooled to 0° C. and treated with 4-(4-methanesulfonyl-phenoxy)-benzo[b]thiophene-6-carboxylic acid ethyl ester (0.58 g, crude product from previous step) in dichloroethane (5 ml). The mixture is 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 (50 ml). Separation of the organic layer followed by evaporation yielded crude product (1.1 g). This was purified by silica gel chromatography (0-20% MeOH/CHCl3) to yield 0.35 g (59%) of 4-(4-methanesulfonyl-phenoxy)-benzo[b]thiophene-6-carboxylic acid (5-methyl-pyridin-2-yl)-amide. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.85(s, 1H), 8.69 (s, 1H), 8.22(d, J=8.8, 2H), 8.10 (d, J=8.6, 1H), 8.03 (d, J=5.5, 1H), 7.94 (d, J=8.8, 2H), 7.76 (d, J=1.3, 1H), 7.67 (dd, J=9.0, 2.0, 1H), 7.38 (d, J=5.5, 1H), 7.26 (d, J=8.8, 2H), 3.21 (s, 3H0, 2.28 (s, 3H). LRMS for C22H18N2O4S2 m/z 439 (M+H)+. Anal. Calcd. for C22H18N2O4S2 C, 60.26;H, 4.14; N, 6.39; Found: C, 60.58; H, 4.23; N, 6.22.

Workup

  1. customrecooled to 0° C.
  2. temperatureto warm to room temperature
  3. waitheld at room temperature for 8 h
  4. customThe reaction was quenched by the drop wise addition of MeOH (2 mL) at 0 C
  5. customSeparation of the organic layer
  6. customfollowed by evaporation
  7. customyielded crude product (1.1 g)
  8. customThis was purified by silica gel chromatography (0-20% MeOH/CHCl3)

Sources & evidence

ORD record
ord-ea42fc6ff13a45ae8c54080f6c86061d
Source dataset
uspto-grants-2012_02
Patent number
US08119624B2

Reaction notes

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