Diisopropylethylamine → 2-Chloro-N-(4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-isonicotinamide

HRID 1167732Notes

Reaction equation

HRID 1167732 reaction equation
[CH3:1][O:2][C:3]1[C:8]2[N:9]=[C:10]([NH2:12])[S:11][C:7]=2[C:6]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)=[CH:5][CH:4]=1.C(N(C(C)C)C(C)C)C.[Cl:28][C:29]1[CH:30]=[C:31]([CH:35]=[CH:36][N:37]=1)[C:32](Cl)=[O:33]>C1COCC1.ClCCl>[Cl:28][C:29]1[CH:30]=[C:31]([CH:35]=[CH:36][N:37]=1)[C:32]([NH:12][C:10]1[S:11][C:7]2[C:6]([N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[CH:5][CH:4]=[C:3]([O:2][CH3:1])[C:8]=2[N:9]=1)=[O:33]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 28000032-Chloropyridine-4-carbonyl chlorideHCID 114028614-Methoxy-7-morpholinobenzo[d]thiazol-2-amine

Product 1

HCID 113156942-Chloro-N-(4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-isonicotinamideYield 59.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 10.8 g (40.8 mmol) 4-methoxy-7-morpholin-4-yl-benzothiazol-2-ylamine and 17.3 ml (102 mmol) N-ethyldiisopropylamine in 500 ml THF at 5° C. was added dropwise over 90 minutes a solution of 7.90 g (44.9 mmol) 2-chloro-isonicotinoyl chloride in 250 ml dichloromethane and stirring continued at room temperature for 16 h. The reaction mixture was then quenched by addition of 30 ml methanol and concentrated in vacuo. The residue was then resuspended in ethyl acetate and washed sequentially with saturated sodium bicarbonate solution, 0.5 M hydrochloric acid and saturated brine. The organic phase was then dried over sodium sulfate and concentrated in Vacuo to ca 100 ml. The resulting suspension was then left standing at room temperature for 72 h and then 100 ml ether was added and the suspension stirred for 1 hour at room temperature. The crystals were collected by filtration and dried in vacuo to afford 9.79 g (59%) 2-chloro-N-(4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-isonicotinamide as a brown crystalline solid. ES-MS m/e (%): 429 (M{37Cl}+Na+, 11), 427 (M{35Cl}+Na+, 30). 407 (M{37Cl}+H+, 30), 405 (M{35Cl}+H+, 100).

Workup

  1. customThe reaction mixture was then quenched by addition of 30 ml methanol
  2. concentrationconcentrated in vacuo
  3. washwashed sequentially with saturated sodium bicarbonate solution, 0.5 M hydrochloric acid and saturated brine
  4. dry with materialThe organic phase was then dried over sodium sulfate
  5. concentrationconcentrated in Vacuo to ca 100 ml
  6. waitThe resulting suspension was then left
  7. waitstanding at room temperature for 72 h
  8. addition100 ml ether was added
  9. stirringthe suspension stirred for 1 hour at room temperature
  10. filtrationThe crystals were collected by filtration
  11. customdried in vacuo

Sources & evidence

ORD record
ord-d915ecaa19a24033846f1913eef1213b
Source dataset
uspto-grants-2003_09
Patent number
US06620811B2

Reaction notes

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