1-(4-(6-Aminopyrimidin-4-yloxy)-3-fluorophenyl)-3-(2-(4-fluorophenyl)acetyl)thiourea → 1-[4-(2-Aminopyridin-4-yloxy)-3-fluorophenyl]-3-[(4-fluorophenyl)acetyl]thiourea

HRID 1670233Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1670233
N[C:2]1[N:7]=[CH:6][N:5]=[C:4]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]([NH:18][C:19](=[O:28])[CH2:20][C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=3)=[S:17])=[CH:11][C:10]=2[F:29])[CH:3]=1.F[C:31]1C=CC(CC(N=C=S)=O)=CC=1>C(Cl)Cl>[NH2:5][C:6]1[CH:31]=[C:4]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]([NH:18][C:19](=[O:28])[CH2:20][C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=3)=[S:17])=[CH:11][C:10]=2[F:29])[CH:3]=[CH:2][N:7]=1

Komponenten

4

Edukt 2

HCID 115389121-(4-(6-Aminopyrimidin-4-yloxy)-3-fluorophenyl)-3-(2-(4-fluorophenyl)acetyl)thiourea2×HCID 231532482-(4-Fluorophenyl)acetyl isothiocyanate

Produkt 1

HCID 231530171-[4-(2-Aminopyridin-4-yloxy)-3-fluorophenyl]-3-[(4-fluorophenyl)acetyl]thioureaAusbeute 38,6 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

4-Fluorophenylacetylchloride (Aldrich, 0.017 mL, 0.126 mmol, 2.5 eq) was added to a solution of sodium thiocyanate (0.014 g, 0.176 mmol, 3.5 eq) in ethyl acetate (1.0 mL) at room temperature and the reaction mixture was stirred for 1.5 h to afford a 2-(4-fluorophenyl)ethanoyl isothiocyanate solution (0.126 M). 4-(4-Amino-2-fluorophenoxy)pyridin-2-amine (Compound B of Example 24, 0.011 g, 0.050 mmol, 1.0 eq) was dissolved in CH2Cl2 (1.0 mL) and 2-(4-fluorophenyl)ethanoyl isothiocyanate (0.126 M, 0.50 mL, 0.063 mmol, 1.3 eq) was added and the reaction mixture was stirred at room temperature for 20 h. The reaction mixture was concentrated in vacuo and the resulting residue was purified by silica gel flash chromatography (Merck, 40-63 μM, 230-240 mesh, eluting 0-6% MeOH in CHCl3) to afford the title compound (0.008 g, 38%) as a solid. 1H NMR (CD3OD) δ 7.85-7.95 (m, 1H), 7.67-7.69 (m, 1H), 7.13-7.28 (m, 4H), 6.95-7.00 (m, 2H), 6.05-6.15 (m, 1H), 5.90-5.91 (m, 1H), 3.65 (s, 2H); MS (ESI+) m/z 415 (M+H)+; HRMS (ESI+) calculated: 415.1040. found: 415.1041.

Aufarbeitung

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthe resulting residue was purified by silica gel flash chromatography (Merck, 40-63 μM, 230-240 mesh, eluting 0-6% MeOH in CHCl3)

Quellen und Nachweise

ORD-Eintrag
ord-1e6863441a1c4127b3318bbea5895db4
Quelldatensatz
uspto-grants-2011_08
Patentnummer
US07989477B2

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