5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-benzothiazole → 6-(benzo[d]thiazol-5-yl)-N-(3,4-dimethoxyphenyl)imidazo[1,2-a]pyrazin-8-amine

HRID 404543Notes

Reaction equation

HRID 404543 reaction equation
Br[C:2]1[N:3]=[C:4]([NH:11][C:12]2[CH:17]=[C:16]([O:18][CH3:19])[C:15]([O:20][CH3:21])=[C:14](OC)[CH:13]=2)[C:5]2[N:6]([CH:8]=[CH:9][N:10]=2)[CH:7]=1.CC1(C)C(C)(C)OB([C:32]2[CH:33]=[CH:34][C:35]3[S:39][CH:38]=[N:37][C:36]=3[CH:40]=2)O1>C(=O)([O-])[O-].[Na+].[Na+].O1CCOCC1.CO.C(OCC)(=O)C.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[S:39]1[C:35]2[CH:34]=[CH:33][C:32]([C:2]3[N:3]=[C:4]([NH:11][C:12]4[CH:13]=[CH:14][C:15]([O:20][CH3:21])=[C:16]([O:18][CH3:19])[CH:17]=4)[C:5]4[N:6]([CH:8]=[CH:9][N:10]=4)[CH:7]=3)=[CH:40][C:36]=2[N:37]=[CH:38]1

Participants

7

Reactant 2

HCID 467390305-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-benzothiazoleHCID 866449836-bromo-N-(3,4,5-trimethoxyphenyl)imidazo[1,2-a]pyrazin-8-amine

Product 1

HCID 462346246-(benzo[d]thiazol-5-yl)-N-(3,4-dimethoxyphenyl)imidazo[1,2-a]pyrazin-8-amineYield 70%

Reagents, catalysts & solvents 4

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 10340Sodium CarbonateSolventHCID 312751,4-DioxaneSolventHCID 21584119Ethylacetate methanolSolvent

Procedure

A mixture of 6-bromo-N-(3,4-dimethoxyphenyl)imidazo[1,2-a]pyrazin-8-amine (2) (209 mg, 0.601 mmol), and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[d]thiazole (3) (180 mg, 0.689 mmol) in 1 M aqueous sodium carbonate (0.76 mL) and 1,4-dioxane (2.4 mL) was sparged with nitrogen while stirring for 5 min. Tetrakis(triphenyl-phosphine) palladium(0) (69 mg, 0.06 mmol) was then added and the resulting mixture reacted under microwave irradiation at 135° C. for 30 min. After this time, the reaction was cooled to ambient temperature, diluted with 1:9 methanol/ethyl acetate (75 mL), and washed with water (50 mL) then brine (50 mL). The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by chromatography (silica, gradient 0% to 10% methanol in methylene chloride) to afford 6-(benzo[d]thiazol-5-yl)-N-(3,4-dimethoxyphenyl)imidazo[1,2-a]pyrazin-8-amine (4) (169 mg, 70%) as an off-white solid: mp 179-181° C.; 1H NMR (300 MHz, DMSO-d6) δ 9.56 (s, 1H), 9.45 (s, 1H), 8.78 (s, 1H), 8.76 (d, 1H, J=1.2 Hz), 8.26 (d, 1H, J=8.7 Hz), 8.14 (m, 2H), 8.00 (s, 1H), 7.66 (s, 1H), 7.58 (dd, 1H, J=8.7, 2.4 Hz), 6.99 (d, 1H, J=8.7 Hz), 3.87 (s, 3H), 3.76 (s, 3H); MS m/z 404.6 [M+H]+; HPLC, 6.475 min, 98.6% (AUC).

Workup

  1. customwas sparged with nitrogen
  2. customthe resulting mixture reacted under microwave irradiation at 135° C. for 30 min
  3. washwashed with water (50 mL)
  4. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue was purified by chromatography (silica, gradient 0% to 10% methanol in methylene chloride)

Sources & evidence

ORD record
ord-e96c5e6417a445a8a1fd560cfb0216fa
Source dataset
uspto-grants-2014_06
Patent number
US08748607B2

Reaction notes

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