Diisopropylethylamine → 2-bromo-N-[4-methoxy-7-(tetrahydro-pyran-2-yl)-benzothiazol-2-yl]-isonicotinamide

HRID 1582164Notes

Reaction equation

HRID 1582164 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][N:10]=1)[C:5]([OH:7])=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)C(C)C)C.[CH3:44][O:45][C:46]1[C:51]2[N:52]=[C:53]([NH2:55])[S:54][C:50]=2[C:49]([CH:56]2[CH2:61][CH2:60][CH2:59][CH2:58][O:57]2)=[CH:48][CH:47]=1.C(=O)(O)[O-].[Na+]>C1COCC1.O1CCOCC1.CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][N:10]=1)[C:5]([NH:55][C:53]1[S:54][C:50]2[C:49]([CH:56]3[CH2:61][CH2:60][CH2:59][CH2:58][O:57]3)=[CH:48][CH:47]=[C:46]([O:45][CH3:44])[C:51]=2[N:52]=1)=[O:7]

Participants

9

Reactant 5

HCID 81531DiisopropylethylamineHCID 2227012-Bromoisonicotinic acidHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 227195344-Methoxy-7-(tetrahydro-pyran-2-yl)-benzothiazol-2-ylamine

Product 1

HCID 103104522-bromo-N-[4-methoxy-7-(tetrahydro-pyran-2-yl)-benzothiazol-2-yl]-isonicotinamideYield 29.5%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent

Procedure

To a stirred solution of 0.99 g (4.92 mmol) 2-bromo-isonicotinic acid in 40 ml THF were added 2.16 g (5.67 mmol) HATU and 0.97 ml (5.67 mmol) N-ethyldiisopropylamine and stirring continued at room temperature for 1 h. A solution of 1.00 g (3.78 mmol) 4-methoxy-7-(tetrahydro-pyran-2-yl)-benzothiazol-2-ylamine in 20 ml dioxane and 4 ml DMF was then added and stirring continued at room temperature for 48 h. The reaction mixture was then poured into aqueous sodium bicarbonate solution and extracted three times with dichloromethane. The combined organic phases were washed with 1 M hydrochloric acid, then dried over sodium sulfate and concentrated in vacuo. Flash chromatography (acetone/hexane 1/4) followed by trituration in ether afforded 500 mg (29%) 2-bromo-N-[4-methoxy-7-(tetrahydro-pyran-2-yl)-benzothiazol-2-yl]-isonicotinamide as a light yellow crystalline solid. ES-MS m/e (%): 450 (M{81Br}+H+, 100), 448 (M{79Br}+H+, 80).

Workup

  1. stirringstirring
  2. waitcontinued at room temperature for 48 h
  3. extractionextracted three times with dichloromethane
  4. washThe combined organic phases were washed with 1 M hydrochloric acid
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-23fe45ec78f048dc8a93fe2e5c26eda9
Source dataset
uspto-grants-2004_05
Patent number
US06734179B2

Reaction notes

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