Ethyl isocyanate → 1-{4-[4-(1,5-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl-3'-yl]-benzyl}-3-ethyl-urea

HRID 220596

Reaktionsgleichung

[CH3:1][N:2]1[C:6]([CH3:7])=[C:5]([CH2:8][N:9]2[CH2:14][CH2:13][N:12]([C:15]3[C:20]([C:21]4[CH:28]=[CH:27][C:24]([CH2:25][NH2:26])=[CH:23][CH:22]=4)=[N:19][CH:18]=[CH:17][N:16]=3)[CH2:11][CH2:10]2)[CH:4]=[N:3]1.[N:29]([CH2:32][CH3:33])=[C:30]=[O:31]>O1CCCC1.CN(C)C1C=CN=CC=1>[CH3:1][N:2]1[C:6]([CH3:7])=[C:5]([CH2:8][N:9]2[CH2:10][CH2:11][N:12]([C:15]3[C:20]([C:21]4[CH:22]=[CH:23][C:24]([CH2:25][NH:26][C:30]([NH:29][CH2:32][CH3:33])=[O:31])=[CH:27][CH:28]=4)=[N:19][CH:18]=[CH:17][N:16]=3)[CH2:13][CH2:14]2)[CH:4]=[N:3]1

Komponenten

Reaktionsbedingungen

Temperatur: 50 °C

Versuchsvorschrift

Dissolve 4-[4-(1,5-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl-3′-yl]-benzylamine (0.35 g, 0.93 mmol) in tetrahydrofuran (6 mL). Add isocyanato-ethane (1 eq., 0.06 g, 0.84 mmol). Add 4-(dimethylamino)pyridine (0.05 eq., 0.005 g, 0.043 mmol). Heat at 50° C. for 17 hr. Purify by normal phase chromatography with eluent 4% 7N ammonia-methanol/ethyl acetate to give 1-{4-[4-(1,5-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl-3′-yl]-benzyl}-3-ethyl-urea (0.252 g, 62%). MS (ES): m/z=449.3[M+H]. Dissolve (0.252 g, 0.56 mmol) in acetonitrile (1 mL) and water (4 mL). Add aq. 1 N HCl (1 eq., 0.56 mmol, 0.56 mL). Freeze the solution to −78° C. in a dry-ice/acetone bath. Place the solution in the lyophilizer for 48 hr. to give the title compound (0.250 g, 97% yield). MS (ES): m/z=449.3 [M+H].

Aufarbeitung

customPurify by normal phase chromatography with eluent 4% 7N ammonia-methanol/ethyl acetate

Quellen und Nachweise

ORD-Eintrag: ord-4b82ab2420524910bb0f6b24efa29aaa
Quelldatensatz: uspto-grants-2012_06
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US08202873B2

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