Sodium Carbonate → HCID 44176976, compound

HRID 2090161Notes

Reaction equation

HRID 2090161 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:10]=[CH:11][C:12]3[S:16][C:15]([CH3:17])=[N:14][C:13]=3[CH:18]=2)[CH:5]=[N:4][CH:3]=1.[N:19]1[CH:24]=[CH:23][C:22](B(O)O)=[CH:21][CH:20]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.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>[CH3:17][C:15]1[S:16][C:12]2[CH:11]=[CH:10][C:9]([NH:8][C:6]3[CH:5]=[N:4][CH:3]=[C:2]([C:22]4[CH:23]=[CH:24][N:19]=[CH:20][CH:21]=4)[N:7]=3)=[CH:18][C:13]=2[N:14]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 2734379(Pyridin-4-yl)boronic acidHCID 86652756HCID 86652756, compound

Product 1

HCID 44176976HCID 44176976, compoundYield 86.7%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 18180031Water 1,2-dimethoxyethaneSolvent

Procedure

A mixture of 2,6-dichloropyrazine (0.150 g, 1.006 mmol), 5-amino-2-methylbenzothiazole (0.250 g, 1.51 mmol), BINAP (0.0137 g, 0.02215 mmol), sodium tertiary butoxide (0.136 g, 1.409 mmol) and palladium acetate (0.005 g, 0.02215 mmol) in toluene (8 mL) was heated at 85° C. for 16 h under nitrogen. CH2Cl2 was added, the reaction mixture was filtered through Celite, and the solvent was evaporated. The residue was purified by column chromatography (5% methanol in CH2Cl2 as eluent) to give 0.180 g (65%) of intermediate (6-chloro-pyrazin-2-yl)-(2-methyl-benzothiazol-5-yl)-amine. 1H NMR (CDCl3) δ 7.59-7.54 (d, J=15.6 Hz, 2H), 7.38 (s, 1H), 7.19-7.16 (d, J=8.65 Hz, 1H), 6.98-6.95 (d, J=8.41 Hz, 1H), 6.71 (brs, 1H, NH), 2.31 (s, 3H, CH3); MS (API-ES/Positive); m/z: 277 (M+H)+. A mixture of (6-chloro-pyrazin-2-yl)-(2-methyl-benzothiazol-5-yl)-amine (0.075 g, 0.271 mmol), pyridine-4-boronic acid (0.040 g, 0.326 mmol), sodium carbonate (0.143 g, 1.35 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.0156 g, 0.0135 mmol) in DME:water (3:2, 5 mL) was heated at reflux for 20 h. The reaction mixture was concentrated under reduced pressure and the residue obtained was extracted with dichloromethane. The organic layer was washed with water, brine, dried over sodium sulfate and concentrated. The crude product was purified by flash chromatography (5% methanol in CH2Cl2 as eluent) to yield 2-methyl-N-(6-pyridin-4-ylpyrazin-2-yl)-1,3-benzothiazol-5-amine (0.075 g, 86.5%) as a yellow solid. 1H NMR (CD3OD) δ 8.82 (m, 3H), 8.72 (s, 1H), 8.45-8.44 (m, 2H), 8.35 (s, 1H), 7.92-7.90 (d, J=8.67 Hz, 1H), 7.61-7.59 (dd, J=10.63, 1.94 Hz, 1H), 2.89 (s, 3H, CH3); MS (API-ES/Positive); m/z: 320 (M+H)+.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 20 h
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. customthe residue obtained
  5. extractionwas extracted with dichloromethane
  6. washThe organic layer was washed with water, brine
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated
  9. customThe crude product was purified by flash chromatography (5% methanol in CH2Cl2 as eluent)

Sources & evidence

ORD record
ord-e83cf4c5e338462a9a0dea0f041550c2
Source dataset
uspto-grants-2013_05
Patent number
US08436171B2

Reaction notes

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