Methanol → 2-chloro-N-(4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-6-methyl-isonicotinamide

HRID 1063058Notes

Reaction equation

HRID 1063058 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]=[C:36]([CH3:38])[N:37]=1)[C:32](Cl)=[O:33].CO>C1COCC1.ClCCl>[Cl:28][C:29]1[CH:30]=[C:31]([CH:35]=[C:36]([CH3:38])[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

7

Reactant 4

HCID 887MethanolHCID 81531DiisopropylethylamineHCID 27821302-Chloro-6-methylpyridine-4-carbonyl chlorideHCID 114028614-Methoxy-7-morpholinobenzo[d]thiazol-2-amine

Product 1

HCID 222831702-chloro-N-(4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-6-methyl-isonicotinamideYield 76.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
5 °C

Procedure

To a stirred suspension of 4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl-amine (13.3 g, 50.1 mmol) in THF (700 ml) was added N-ethyldiisopropylamine (21.3 ml, 125 mmol). The mixture was then cooled to 5° C. and a solution of 2-chloro-6-methyl-isonicotinoyl chloride (10.5 g, 55.1 mmol) in dichloromethane (350 ml) was added dropwise over 2 hours. The reaction mixture was then stirred overnight at 20° C. To this mixture was added methanol (40 ml) and stirring continued for ten minutes. The mixture was then concentrated in vacuo and the residue partitioned between ethyl acetate and saturated sodium bicarbonate solution. The organic phases were then dried over Na2SO4 and the solvent evaporated. The crude product was then chromatographed over SiO2 (Merck 230-400 mesh) eluting with CH2Cl2/MeOH (98:2), the product fractions were pooled and the solvent evaporated, to afford the title compound as a brown solid (16.0 g, 76% yield), MS: m/e=421 (M{37Cl}+H+), 419 (M{35Cl}+H+).

Workup

  1. stirringstirring
  2. waitcontinued for ten minutes
  3. concentrationThe mixture was then concentrated in vacuo
  4. customthe residue partitioned between ethyl acetate and saturated sodium bicarbonate solution
  5. dry with materialThe organic phases were then dried over Na2SO4
  6. customthe solvent evaporated
  7. customThe crude product was then chromatographed over SiO2 (Merck 230-400 mesh)
  8. washeluting with CH2Cl2/MeOH (98:2)
  9. customthe solvent evaporated

Sources & evidence

ORD record
ord-8b861b5a1373406ebbf22501371df204
Source dataset
uspto-grants-2005_11
Patent number
US06963000B2

Reaction notes

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