5-Bromo-2-methylpyridine → 6,6-Dimethyl-2-[6-(6-methylpyridin-3-ylamino)-2,3-dihydrobenzo[1,4]oxazin-4-yl]-6,7-dihydro[1,3]thiazolo[5,4-c]pyridin-4(5h)-one

HRID 885965Notes

Reaction equation

HRID 885965 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]2[O:10][CH2:9][CH2:8][N:7]([C:11]3[S:12][C:13]4[C:14](=[O:22])[NH:15][C:16]([CH3:21])([CH3:20])[CH2:17][C:18]=4[N:19]=3)[C:6]=2[CH:23]=1.Br[C:25]1[CH:26]=[CH:27][C:28]([CH3:31])=[N:29][CH:30]=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:20][C:16]1([CH3:21])[NH:15][C:14](=[O:22])[C:13]2[S:12][C:11]([N:7]3[C:6]4[CH:23]=[C:2]([NH:1][C:25]5[CH:30]=[N:29][C:28]([CH3:31])=[CH:27][CH:26]=5)[CH:3]=[CH:4][C:5]=4[O:10][CH2:9][CH2:8]3)=[N:19][C:18]=2[CH2:17]1

Participants

6

Reactant 3

HCID 12010205-Bromo-2-methylpyridineHCID 23676156Sodium t-butoxideHCID 58441690HCID 58441690, compound

Product 1

HCID 671856026,6-Dimethyl-2-[6-(6-methylpyridin-3-ylamino)-2,3-dihydrobenzo[1,4]oxazin-4-yl]-6,7-dihydro[1,3]thiazolo[5,4-c]pyridin-4(5h)-oneYield 28.2%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Procedure

A stirred suspension of Example 42 (0.050 g, 0.15 mmol), 5-bromo-2-methylpyridine (0.052 g, 0.30 mmol), palladium(II) acetate (0.010 g), 2-bis(dicyclohexylphosphino)biphenyl (0.030 g) and sodium tert-butoxide (0.044 g, 0.46 mmol) in toluene (5 mL) was heated to 120° C. in a sealed tube, under microwave irradiation, for 5 h. After cooling to r.t., the reaction mixture was concentrated in vacuo. Purification by preparative HPLC (Method 7), gave the title compound (0.0178 g, 28%) as an off-white solid. δH (CDCl3) 8.30 (1H, s), 7.80 (1H, s), 7.30 (1H, dd, J 8.5 and J 3.0 Hz), 7.10 (1H, d, J 8.5 Hz), 6.90 (1H, d, J 8.5 Hz), 6.80 (1H, dd, J 8.7 and J 2.4 Hz), 5.60 (1H, br. s), 5.20 (1H, br. s), 4.40 (1H, m), 4.10 (2H, m), 2.90 (2H, m), 2.50 (3H, s), 1.40 (6H, s). LCMS (ES+) 422.0 (M+H)+, RT 3.10 minutes (Method 2).

Workup

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. customPurification by preparative HPLC (Method 7)

Sources & evidence

ORD record
ord-3def91e6cec4449ca9c50372f76810c5
Source dataset
uspto-grants-2012_08
Patent number
US08242116B2

Reaction notes

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