Ammonia → 2-(4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2-oxo-2H-chromen-8-yloxy)acetamide

HRID 20678Notes

Reaction equation

HRID 20678 reaction equation
CC[N:3]=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.[Cl:23][C:24]1[CH:25]=[N:26][CH:27]=[C:28]([Cl:49])[C:29]=1[NH:30][C:31]1[C:40]2[C:35](=[C:36]([O:43][CH2:44][C:45]([OH:47])=O)[C:37]([O:41][CH3:42])=[CH:38][CH:39]=2)[O:34][C:33](=[O:48])[CH:32]=1.N>CN(C1C=CN=CC=1)C.C1COCC1.N1C=CC=CC=1>[Cl:23][C:24]1[CH:25]=[N:26][CH:27]=[C:28]([Cl:49])[C:29]=1[NH:30][C:31]1[C:40]2[C:35](=[C:36]([O:43][CH2:44][C:45]([NH2:3])=[O:47])[C:37]([O:41][CH3:42])=[CH:38][CH:39]=2)[O:34][C:33](=[O:48])[CH:32]=1

Participants

8

Reactant 4

HCID 222AmmoniaHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 248497142-(4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2-oxo-2H-chromen-8-yloxy)acetic acid

Product 1

HCID 248498002-(4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2-oxo-2H-chromen-8-yloxy)acetamide

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

EDC.HCl (85.8 mg, 0.37 mmol), HOBt (49.4 mg, 0.37 mmol), and DMAP (cat.) were sequentially added to a solution of 2-(4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2-oxo-2H-chromen-8-yloxy)acetic acid (100 mg, 0.24 mmol, Example 49) and pyridine (10 mL). After 5 min, a saturated solution of ammonia in THF (10 mL) was added, and the reaction was heated at 40° C. overnight. The reaction was allowed to cool to rt, concentrated to remove THF, and then 2N HCl was added to pH=3. The precipitate was filtered, washed with water, and dried. The crude product was refluxed in ethyl acetate (20 mg/mL) for 10 min, sonicated to break up large particles, refluxed for another 10 min, and then let stand overnight. Filtration and drying gave 2-(4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2-oxo-2H-chromen-8-yloxy)acetamide: 1H NMR (400 MHz, DMSO-d6): δ 9.58 (br s, 1H), 8.79 (s, 2H), 7.97 (d, 1H), 7.57 (s, 1H), 7.41 (s, 1H), 7.23 (d, 1H), 4.62 (s, 1H), 4.40 (s, 2H), 3.94 (s, 3H); MS (ESI): 409.8.

Workup

  1. temperatureto cool to rt
  2. concentrationconcentrated
  3. customto remove THF
  4. addition2N HCl was added to pH=3
  5. filtrationThe precipitate was filtered
  6. washwashed with water
  7. customdried
  8. temperatureThe crude product was refluxed in ethyl acetate (20 mg/mL) for 10 min
  9. customsonicated
  10. temperaturerefluxed for another 10 min
  11. waitlet stand overnight
  12. filtrationFiltration
  13. customdrying

Sources & evidence

ORD record
ord-9874ad4671df4ba7ad2eadfd6a3acddd
Source dataset
uspto-grants-2010_06
Patent number
US07745646B2

Reaction notes

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