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 2096270Notes

Reaction equation

HRID 2096270 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-d2a4b1302e114f1d916abcb84b5cfda6
Source dataset
uspto-grants-2013_05
Patent number
US08450321B2

Reaction notes

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