Water → 2-(6-(1-benzyl-1H-pyrazol-4-yl)-2H-benzo[b][1,4]oxazin-4(3H)-yl)-6,6-dimethyl-6,7-dihydrothiazolo[5,4-c]pyridin-4(5H)-one

HRID 885960Notes

Reaction equation

HRID 885960 reaction equation
Br[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[CH2:14]C(C)(C)N[C:17](=O)[C:18]=4[N:19]=3)[C:6]=2[CH:23]=1.[CH2:24]([N:31]1[CH:35]=[C:34](B2OC(C)(C)C(C)(C)O2)[CH:33]=[N:32]1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C([O-])([O-])=O.[K+].[K+].[OH2:51]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C1COCC1.CCOC(C)=O>[CH2:24]([N:31]1[CH:35]=[C:34]([C:2]2[CH:3]=[CH:4][C:5]3[O:10][CH2:9][CH2:8][N:7]([C:11]4[S:12][C:13]5[C:14](=[O:51])[NH:7][C:6]([CH3:23])([CH3:5])[CH2:17][C:18]=5[N:19]=4)[C:6]=3[CH:23]=2)[CH:33]=[N:32]1)[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1

Participants

8

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 27347711-Benzyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 685972362-(6-Bromo-2,3-dihydrobenzo[1,4]oxazin-4-yl)-6,6-dimethyl-6,7-dihydro-[1,3]thiazolo[5,4-d]pyridin-4(5h)-one

Product 1

HCID 445807222-(6-(1-benzyl-1H-pyrazol-4-yl)-2H-benzo[b][1,4]oxazin-4(3H)-yl)-6,6-dimethyl-6,7-dihydrothiazolo[5,4-c]pyridin-4(5H)-oneYield 68%

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A stirred solution of Example 39 (0.051 g, 0.129 mmol), 1-benzyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (0.049 g, 0.173 mmol), K2CO3 (0.054 g, 0.388 mmol), tetra-n-butylammonium bromide (0.124 g, 0.385 mmol), tetrakis-(triphenylphosphine)palladium(0) (0.010 g, 0.009 mmol) and H2O (0.5 mL) in THF (1 mL) was heated to 125° C. under microwave irradiation for 1 h. The reaction mixture was diluted with EtOAc and washed with water and brine. The organic fractions were dried (MgSO4), filtered and concentrated in vacuo. The crude material was triturated with Et2O to give the title compound (0.041 g, 68%) as a beige solid. δH (CDCl3) 8.03 (1H, d, J 1.9 Hz), 7.78 (1H, s), 7.60 (1H, s), 7.40-7.25 (5H, m), 7.18 (1H, dd, J 8.5 and J 2.1 Hz), 6.96 (1H, d, J 8.3 Hz), 5.37 (2H, s), 5.26 (1H, br. s), 4.38-4.32 (2H, m), 4.22-4.16 (2H, m), 2.89 (2H, s), 1.42 (6H, s). LCMS (ES+) 472.0 (M+H)+, RT 3.53 minutes (Method 1).

Workup

  1. washwashed with water and brine
  2. dry with materialThe organic fractions were dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe crude material was triturated with Et2O

Sources & evidence

ORD record
ord-08c3178ca4bb4603b45f155768738a38
Source dataset
uspto-grants-2012_08
Patent number
US08242116B2

Reaction notes

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