Hydrochloric Acid → HCID 131730541, Verbindung

HRID 402031Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 402031
[ClH:1].Cl.[CH2:3]([C:7]1[N:8]=[N:9][C:10]([O:30][CH:31]2[CH2:36][CH2:35][N:34]([CH3:37])[CH2:33][CH2:32]2)=[CH:11][C:12]=1[C:13]1[CH:14]=[CH:15][C:16]([O:23][CH:24]2[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]2)=[C:17]([NH:19][C:20](=O)[CH3:21])[CH:18]=1)[CH2:4][CH2:5][CH3:6].[Cl:38]CC[CH2:41][S:42](Cl)(=[O:44])=[O:43].CCN(C(C)C)C(C)C.[H-].[Na+].Cl>C(Cl)Cl.CN(C1C=CN=CC=1)C.O.CCOC(C)=O.CCOCC>[ClH:38].[ClH:1].[CH2:3]([C:7]1[N:8]=[N:9][C:10]([O:30][CH:31]2[CH2:32][CH2:33][N:34]([CH3:37])[CH2:35][CH2:36]2)=[CH:11][C:12]=1[C:13]1[CH:14]=[CH:15][C:16]([O:23][CH:24]2[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29]2)=[C:17]([N:19]2[CH2:20][CH2:21][CH2:41][S:42]2(=[O:44])=[O:43])[CH:18]=1)[CH2:4][CH2:5][CH3:6]

Komponenten

10

Edukt 5

HCID 313Hydrochloric AcidHCID 154103-Chloropropanesulphonyl chlorideHCID 24758Sodium hydrideHCID 81531DiisopropylethylamineHCID 67373992HCID 67373992, Verbindung

Produkt 1

HCID 131730541HCID 131730541, VerbindungAusbeute 28,4 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 3283Diethyl EtherLösungsmittelHCID 6344DichloromethaneLösungsmittel2×HCID 22728543Water ethylacetateLösungsmittel

Versuchsvorschrift

To a solution of 5-[3-butyl-6-(1-methyl-piperidin-4-yloxy)-pyridazin-4-yl]-2-cyclohexyloxy-phenylamine (Example 62, 0.2 mmol, 88 mg) in dry DCM (1.0 mL) was added 3-chloropropanesulfonyl chloride (0.4 mmol, 71 mg), DIEA (0.4 mmol, 70 μL), and DMAP (10 mg). And the mixture was stirred at room temperature for 1 hour then condensed. It was then diluted with water/EtOAc. The solvent was removed in vacuo and dried under vacuum over night. The residue was dissolved in dry THF (1.0 mL) at 0° C., NaH (60% dispersion in mineral oil, 0.8 mmol, 32 mg) was added and the mixture was heated at 50° C. for 4 hours. It was then poured into ice-water and extracted with ethyl acetate. The organic layers combined, condensed and the residue was purified by silica gel chromatography (DCM to DCM+10% 2N NH3 in MeOH) to give a colorless sticky solid, which was dissolved in DCM (1.0 mL), 2N HCl in ether (1.0 mL) was added, kept at room temperature for 10 min, condensed, triturated with hexanes to provide the title compound (35 mg). LCMS: m/z 544 [M+1]. 1H NMR (400 MHz, CD3OD): δ 7.70 and 7.81 (1H, s), 7.01-7.12 (3H, m), 5.37-5.56 (1H, m), 4.52-4.58 (1H, m), 3.21-3.69 (8H, m), 3.06-3.13 (2H, m), 2.93 (3H, s), 1.92-2.59 (8H, m), 1.27-1.82 (12H, m), 0.80 (3H, t).

Aufarbeitung

  1. customcondensed
  2. customThe solvent was removed in vacuo
  3. customdried under vacuum over night
  4. dissolutionThe residue was dissolved in dry THF (1.0 mL) at 0° C.
  5. temperaturethe mixture was heated at 50° C. for 4 hours
  6. extractionextracted with ethyl acetate
  7. customcondensed
  8. customthe residue was purified by silica gel chromatography (DCM to DCM+10% 2N NH3 in MeOH)
  9. customto give a colorless sticky solid, which
  10. waitkept at room temperature for 10 min
  11. customcondensed
  12. customtriturated with hexanes

Quellen und Nachweise

ORD-Eintrag
ord-1fa2a3273bfa43bb996d5d70448df1dd
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08741900B2

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