4-Methylmorpholine → 2-bromo-N-{4-methoxy-7-[methyl-(tetrahydro-pyran-4-yl)-amino]-benzothiazol-2-yl}-isonicotinamide

HRID 51901

Reaction equation

HRID 51901 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.CN1CCOCC1.[CH3:42][O:43][C:44]1[C:49]2[N:50]=[C:51]([NH2:53])[S:52][C:48]=2[C:47]([N:54]([CH3:61])[CH:55]2[CH2:60][CH2:59][O:58][CH2:57][CH2:56]2)=[CH:46][CH:45]=1>C1COCC1.C(OCC)(=O)C>[Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][N:10]=1)[C:5]([NH:53][C:51]1[S:52][C:48]2[C:47]([N:54]([CH3:61])[CH:55]3[CH2:56][CH2:57][O:58][CH2:59][CH2:60]3)=[CH:46][CH:45]=[C:44]([O:43][CH3:42])[C:49]=2[N:50]=1)=[O:7]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 2227012-Bromoisonicotinic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 227369724-methoxy-N7-methyl-N7-(tetrahydro-pyran-4-yl)-benzothiazole-2,7-diamine

Product 1

HCID 227369992-bromo-N-{4-methoxy-7-[methyl-(tetrahydro-pyran-4-yl)-amino]-benzothiazol-2-yl}-isonicotinamideYield 63%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 103 mg (0.51 mmol) 2-bromo-isonicotinic acid in 3 ml THF were added 204 mg (0.53 mmol) HATU and 0.11 ml (1.02 mmol) N-methylmorpholine and stirring continued at 30° C. for 7 h. 75 mg (0.26 mmol) 4-methoxy-N7-methyl-N7-(tetrahydro-pyran-4-yl)-benzothiazole-2,7-diamine was then added and stirring continued at 40° C. for 16 h. The reaction mixture was then diluted with ethyl acetate and washed sequentially with saturated sodium bicarbonate solution and brine. The organic phase was dried over sodium sulfate and concentrated in vacuo. Flash chromatography (methanol/dichloromethane) followed by trituration in ether/pentane afforded 77 mg (63%) 2-bromo-N-{4-methoxy-7-[methyl-(tetrahydro-pyran-4-yl)-amino]-benzothiazol-2-yl}-isonicotinamide as a white crystalline solid. ES-MS m/e (%): 479 (M{81Br}+H+, 100), 477 (M{79Br}+H+, 95).

Workup

  1. stirringstirring
  2. waitcontinued at 40° C. for 16 h
  3. washwashed sequentially with saturated sodium bicarbonate solution and brine
  4. dry with materialThe organic phase was dried over sodium sulfate
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-39592673635c4012b2c39da7b52f706e
Source dataset
uspto-grants-2004_03
Patent number
US06713499B2

Linked notes

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