Morpholine → 4-{6-Iodo-3-[(morpholin-4-yl)carbonyl]indazol-1-yl}pyrimidin-2-amine

HRID 1398600Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1398600
[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([I:17])[CH:15]=3)[C:10]([C:18]([OH:20])=O)=[N:9]2)[CH:5]=[CH:4][N:3]=1.S(Cl)(Cl)=O.[NH:25]1[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1.C(=O)([O-])[O-].[Na+].[Na+]>C(Cl)Cl.CN(C=O)C>[I:17][C:14]1[CH:15]=[C:16]2[C:11]([C:10]([C:18]([N:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)=[O:20])=[N:9][N:8]2[C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH2:1])[N:7]=2)=[CH:12][CH:13]=1

Komponenten

7

Edukt 4

HCID 8083MorpholineHCID 10340Sodium CarbonateHCID 24386Thionyl ChlorideHCID 681816001-(2-Aminopyrimidin-4-yl)-6-iodoindazole-3-carboxylic acid

Produkt 1

HCID 681816904-{6-Iodo-3-[(morpholin-4-yl)carbonyl]indazol-1-yl}pyrimidin-2-amine

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideKatalysatorHCID 6344DichloromethaneLösungsmittel2×

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

To a solution of 1-(2-aminopyrimidin-4-yl)-6-iodo-1H-indazole-3-carboxylic acid (3.00 g, 7.87 mmol) in dry DCM (40 mL) was introduced thionyl chloride (6.85 mL, 94.46 mmol) and DMF (3 drops, cat.). The reaction mixture was warmed to 50° C. for 1 hr. After cooling to RT, the reaction mixture was concentrated in vacuo. The residue was re-dissolved in dry DCM (20 mL) and concentrated in vacuo (twice). After suspending the residue in dry DCM (30 mL), the solution was cooled to 0° C. under an atmosphere of nitrogen, and morpholine (1.37 mL, 15.74 mmol) added dropwise. The reaction mixture was warmed to RT for 16 hr. Following dilution with DCM (25 mL), 2M aqueous sodium carbonate (35 mL) was introduced. The resulting precipitate was collected by filtration and washed on the filter with DCM (5 mL) and dried. After suspension of the precipitate in 3:1 water/acetonitrile (10 mL), the slurry was collected by filtration and washed on the filter with further 3:1 water/acetonitrile (2×1 mL washes). The filter cake was dried under vacuum to furnish the title compound as an off-white solid: 1H NMR (500 MHz, DMSO) delta 3.41-3.76 (6H, m), 3.85-3.97 (2H, m), 7.05 (1H, d, J=5.5 Hz), 7.18 (2H, s), 7.74 (1H, dd, J=8.4, 1.1 Hz), 7.80 (1H, d, J=8.4 Hz), 8.34 (1H, d, J=5.5 Hz), 9.33 (1H, s); LC-MS: m/z=+450.90 (M+H)+.

Aufarbeitung

  1. temperatureAfter cooling to RT
  2. concentrationthe reaction mixture was concentrated in vacuo
  3. dissolutionThe residue was re-dissolved in dry DCM (20 mL)
  4. concentrationconcentrated in vacuo (twice)
  5. temperaturethe solution was cooled to 0° C. under an atmosphere of nitrogen
  6. temperatureThe reaction mixture was warmed to RT for 16 hr
  7. additionwas introduced
  8. filtrationThe resulting precipitate was collected by filtration
  9. washwashed on the
  10. filtrationfilter with DCM (5 mL)
  11. customdried
  12. additionAfter suspension of the precipitate in 3:1 water/acetonitrile (10 mL)
  13. filtrationthe slurry was collected by filtration
  14. washwashed on the
  15. filtrationfilter with further 3:1 water/acetonitrile (2×1 mL washes)
  16. customThe filter cake was dried under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-f2713e1edab34368a6bd4482ecf728b6
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08901313B2

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