Hydrochloric Acid → HCID 178478933, Verbindung

HRID 246619Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 246619
[F:1][CH:2]([F:40])[O:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH3:13])[N:8]=[C:7]2[C:14]1[N:15]=[C:16]2[C:22]([C:23]([NH:25][C@@H:26]3[CH2:31][CH2:30][C@H:29]([NH:32]C(=O)OC(C)(C)C)[CH2:28][CH2:27]3)=[O:24])=[CH:21][NH:20][C:17]2=[N:18][CH:19]=1.[ClH:41]>O1CCOCC1>[ClH:41].[NH2:32][C@@H:29]1[CH2:28][CH2:27][C@H:26]([NH:25][C:23]([C:22]2[C:16]3=[N:15][C:14]([C:7]4[C:6]5[C:10](=[CH:11][CH:12]=[C:4]([O:3][CH:2]([F:1])[F:40])[CH:5]=5)[N:9]([CH3:13])[N:8]=4)=[CH:19][N:18]=[C:17]3[NH:20][CH:21]=2)=[O:24])[CH2:31][CH2:30]1

Komponenten

4

Edukt 2

HCID 313Hydrochloric AcidHCID 178481759HCID 178481759, Verbindung

Produkt 1

HCID 178478933HCID 178478933, VerbindungAusbeute 29,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

tert-Butyl cis-4-(2-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamido)cyclohexylcarbamate (54 mg, 0.1 mmol) in 3 mL of 1,4-dioxane was added 10 mL of concentrated HCl. The reaction mixture was stirred overnight at 25° C. After evaporation under the reduced pressure, the residue was purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm; inject volume: 3 mL/inj, flow rate: 20 mL/min; wavelength: 214 nm and 254 nm; the gradient conditions are: 40% acetonitrile/60% water (0.1% trifluoroacetic acid V/V) initially, and then proceed to 50% acetonitrile/50% water (0.1% trifluoroacetic acid V/V) in a linear fashion after just 9 min). After concentration, the crude solid was treated with 1N HCl (2 mL), the mixture was stirred for 10 min then evaporated and dried to afford N-(cis-4-aminocyclohexyl)-2-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide hydrochloride (13 mg, 29.5%) as yellow solid. LCMS: (M+H)+=456; 1H NMR (300 MHz, CD3OD): δ 8.96 (s, 1H), 8.22 (s, 1H), 8.01 (d, 1H, J=2.1 Hz), 7.56 (d, 1H, J=9.0 Hz), 7.26 (dd, 1H, J1=9.0 Hz, J2=2.4 Hz), 6.76 (t, 1H, J=74.1 Hz), 4.16-4.14 (m, 1H), 4.11 (s, 3H), 3.17-3.15 (m, 1H), 2.15-2.11 (m, 2H), 1.91-1.78 (m, 4H), 1.60-1.48 (m, 2H).

Aufarbeitung

  1. customAfter evaporation under the reduced pressure
  2. customthe residue was purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm
  3. wait40% acetonitrile/60% water (0.1% trifluoroacetic acid V/V) initially, and then proceed to 50% acetonitrile/50% water (0.1% trifluoroacetic acid V/V) in a linear fashion after just 9 min
  4. concentrationAfter concentration
  5. additionthe crude solid was treated with 1N HCl (2 mL)
  6. stirringthe mixture was stirred for 10 min
  7. customthen evaporated
  8. customdried

Quellen und Nachweise

ORD-Eintrag
ord-f67a042efe8743b5a7f84b580a1db2ae
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658646B2

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