tert-Butyl 2-(chloromethyl)-1H-benzimidazole-1-carboxylate → 2-{[[4-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-butyl]-(1-methyl-1-pyridin-2-yl-ethyl)-amino]-methyl}-benzimidazole-1-carboxylic acid tert-butyl ester

HRID 251080Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 251080
[CH3:1][C:2]([NH:10][CH2:11][CH2:12][CH2:13][CH2:14][N:15]1[C:23](=[O:24])[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[C:16]1=[O:25])([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][N:5]=1)[CH3:3].[C:26]([O:30][C:31]([N:33]1[C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][C:36]=2[N:35]=[C:34]1[CH2:42]Cl)=[O:32])([CH3:29])([CH3:28])[CH3:27]>CC#N.CCN(C(C)C)C(C)C>[C:26]([O:30][C:31]([N:33]1[C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][C:36]=2[N:35]=[C:34]1[CH2:42][N:10]([CH2:11][CH2:12][CH2:13][CH2:14][N:15]1[C:23](=[O:24])[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[C:16]1=[O:25])[C:2]([CH3:1])([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][N:5]=1)[CH3:3])=[O:32])([CH3:29])([CH3:28])[CH3:27]

Komponenten

5

Edukt 2

HCID 15829159tert-Butyl 2-(chloromethyl)-1H-benzimidazole-1-carboxylateHCID 672731322-[4-(1-Methyl-1-pyridin-2-yl-ethylamino)-butyl]-isoindole-1,3-dione

Produkt 1

HCID 672727882-{[[4-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-butyl]-(1-methyl-1-pyridin-2-yl-ethyl)-amino]-methyl}-benzimidazole-1-carboxylic acid tert-butyl ester

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6342AcetonitrileLösungsmittelHCID 81531DiisopropylethylamineLösungsmittel

Versuchsvorschrift

Using General Procedure A: Reaction of 2-[4-(1-methyl-1-pyridin-2-yl-ethylamino)-butyl]-isoindole-1,3-dione in dry CH3CN, N-(tert-butoxycarbonyl)-2-chloromethylbenzimidazole, DIPEA and KI gave 2-{[[4-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-butyl]-(1-methyl-1-pyridin-2-yl-ethyl)-amino]-methyl}-benzimidazole-1-carboxylic acid tert-butyl ester as a white foam. 1H NMR (CDCl3) δ 1.18-1.33 (m, 2H), 1.39-1.54 (m, 2H), 1.52 (s, 6H), 1.71 (s, 9H), 2.65 (t, 2H, J=7.5 Hz), 3.43 (t, 2H, J=7.2 Hz), 4.27 (s, 2H), 7.04 (t, 1H, J=4.8 Hz), 7.19-7.31 (m, 3H), 7.55 (td, 1H, J=7.7, 1.7 Hz), 7.62-7.70 (m, 2H), 7.70-7.78 (m, 2H), 7.81 (dd, 1H, J=6.6, 1.6 Hz), 8.06 (d, 1H, J=8.4 Hz), 8.47 (d, 1H, J=3.9 Hz). Deprotection with H2NNH2.H2O using General Procedure E gave a colorless oil. Conversion to the HBr salt gave COMPOUND 222 as a white solid. 1H NMR (D2O) δ 1.36-1.51 (m, 4H), 1.60 (s, 6H), 2.46-2.59 (m, 2H), 2.72-2.84 (m, 2H), 4.56 (s, 2H), 7.54-7.64 (m, 2H), 7.74-7.84 (m, 2H), 8.03 (t, 1H, J=6.6 Hz), 8.21 (d, 1H, J=8.4 Hz), 8.64 (t, 1H, J=7.8 Hz), 8.85 (d, 1H, J=5.4 Hz); 13C NMR (D2O) δ 23.21, 24.88, 26.01, 39.43, 45.77, 53.70, 63.80, 114.23, 125.75, 126.73, 126.84, 131.03, 142.12, 148.73, 153.74, 160.26; ES-MS m/z 338 (M+H). Anal. Calcd. for C20H27N5.3.0HBr.1.4H2O.0.3C4H10O: C, 40.57; H, 5.75; N, 11.16; Br, 38.19. Found: C, 40.48; H, 5.67; N, 11.01; Br, 38.18.

Quellen und Nachweise

ORD-Eintrag
ord-20681e67d4734d298b33f8b12fb14b91
Quelldatensatz
uspto-grants-2011_01
Patentnummer
US07863293B2

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