Potassium Phosphate, Tribasic → 2-[6-(1,2-Dimethyl-1h-imidazol-5-yl)-2,3-dihydro-4h-1,4-benzoxazin-4-yl]-6,6-dimethyl-6,7-dihydro[1,3]thiazolo[5,4-c]pyridin-4(5h)-one

HRID 885982Notes

Reaction equation

HRID 885982 reaction equation
[CH3:1][C:2]1([CH3:31])[NH:7][C:6](=[O:8])[C:5]2[S:9][C:10]([N:12]3[C:17]4[CH:18]=[C:19](B5OC(C)(C)C(C)(C)O5)[CH:20]=[CH:21][C:16]=4[O:15][CH2:14][CH2:13]3)=[N:11][C:4]=2[CH2:3]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Br[C:41]1[N:45]([CH3:46])[C:44]([CH3:47])=[N:43][CH:42]=1>C1COCC1.O.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:46][N:45]1[C:41]([C:19]2[CH:20]=[CH:21][C:16]3[O:15][CH2:14][CH2:13][N:12]([C:10]4[S:9][C:5]5[C:6](=[O:8])[NH:7][C:2]([CH3:1])([CH3:31])[CH2:3][C:4]=5[N:11]=4)[C:17]=3[CH:18]=2)=[CH:42][N:43]=[C:44]1[CH3:47]

Participants

8

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 72048795-bromo-1,2-dimethyl-1H-imidazoleHCID 584916876,6-dimethyl-2-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-benzo[b][1,4]oxazin-4(3H)-yl)-6,7-dihydrothiazolo[5,4-c]pyridin-4(5H)-one

Product 1

HCID 671866382-[6-(1,2-Dimethyl-1h-imidazol-5-yl)-2,3-dihydro-4h-1,4-benzoxazin-4-yl]-6,6-dimethyl-6,7-dihydro[1,3]thiazolo[5,4-c]pyridin-4(5h)-oneYield 28.7%

Reagents, catalysts & solvents 4

HCID 74236Tetrabutylammonium BromideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
140 °C

Procedure

To a solution of Example 292 (75 mg, 0.17 mmol) in THF (3 mL) and water (1 mL) was added tetra-n-butylammonium bromide (107 mg, 0.34 mmol), potassium phosphate (72 mg, 0.34 mmol), 5-bromo-1,2-dimethyl-1H-imidazole (60 mg, 0.34 mmol) and tetrakis(triphenylphosphine)palladium(0) (20 mg, 0.017 mmol). The reaction was heated at 140° C. under microwave irradiation for 25 minutes. The resulting mixture was partitioned between DCM (50 mL) and water (50 mL); the organic fraction was washed with brine (50 mL), dried (MgSO4), and concentrated in vacuo. The residue was purified by preparative HPLC (Method 7) to yield the title compound (20 mg, 28%) as a white solid. δH (CDCl3) 7.99 (1H, d, J 1.9 Hz), 7.06 (1H, dd, J 8.5 and 1.9 Hz), 7.01 (1H, d, J 8.5 Hz), 6.93 (1H, s), 5.34 (1H, s), 4.40-4.35 (2H, m), 4.19-4.13 (2H, m), 3.57 (3H, s), 2.87 (2H, s), 2.46 (3H, s), 1.40 (6H, s). LCMS (ES+) 410.0 (M+H)+, RT 1.95 minutes (Method 1).

Workup

  1. customThe resulting mixture was partitioned between DCM (50 mL) and water (50 mL)
  2. washthe organic fraction was washed with brine (50 mL)
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by preparative HPLC (Method 7)

Sources & evidence

ORD record
ord-bed36c4dd07149bbbbf8d2756c5008e7
Source dataset
uspto-grants-2012_08
Patent number
US08242116B2

Reaction notes

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