Methylamine → 2-(4-fluorophenyl)-2-(4-(3-fluorophenyl)-4-{2-[(1R,5S)-3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}piperidin-1-yl)-N-methylacetamide

HRID 1992146

Reaktionsgleichung

Reaktionsgleichung von HRID 1992146
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([N:12]2[CH2:17][CH2:16][C:15]([C:38]3[CH:43]=[CH:42][CH:41]=[C:40]([F:44])[CH:39]=3)([CH2:18][CH2:19][N:20]3[C@H:25]4[CH2:26][CH2:27][C@@H:21]3[CH2:22][CH:23]([N:28]3[C:32]5[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=5[N:30]=[C:29]3[CH3:37])[CH2:24]4)[CH2:14][CH2:13]2)[C:9]([OH:11])=O)=[CH:4][CH:3]=1.FC1C=C(C2(CCN3[C@H]4CC[C@@H]3CC(N3C5C=CC=CC=5N=C3C)C4)CC[NH:55][CH2:54]C2)C=CC=1.FC1C=CC(B(O)O)=CC=1.CN.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([N:12]2[CH2:17][CH2:16][C:15]([C:38]3[CH:43]=[CH:42][CH:41]=[C:40]([F:44])[CH:39]=3)([CH2:18][CH2:19][N:20]3[C@H:21]4[CH2:27][CH2:26][C@@H:25]3[CH2:24][CH:23]([N:28]3[C:32]5[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=5[N:30]=[C:29]3[CH3:37])[CH2:22]4)[CH2:14][CH2:13]2)[C:9]([NH:55][CH3:54])=[O:11])=[CH:4][CH:3]=1

Komponenten

6

Edukt 5

HCID 6329MethylamineHCID 2856454-Fluorophenylboronic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 44573338(4-Fluorophenyl)(4-(3-fluorophenyl)-4-{2-[(1R,5S)-3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}piperidin-1-yl)acetic acidHCID 587288151-((1R,5S)-8-{2-[4-(3-fluorophenyl)piperidin-4-yl]ethyl}-8-azabicyclo[3.2.1]oct-3-yl)-2-methyl-1H-benzimidazole

Produkt 1

HCID 103264152-(4-fluorophenyl)-2-(4-(3-fluorophenyl)-4-{2-[(1R,5S)-3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}piperidin-1-yl)-N-methylacetamide

Versuchsvorschrift

(4-Fluorophenyl)(4-(3-fluorophenyl)-4-{2-[(1R,5S)-3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}piperidin-1-yl)acetic acid (prepared from 1-((1R,5S)-8-{2-[4-(3-fluorophenyl)piperidin-4-yl]ethyl}-8-azabicyclo[3.2.1]oct-3-yl)-2-methyl-1H-benzimidazole and 4-fluorophenylboronic acid following the procedure outlined in example 412. (19 mg, 0.032 mmol) was coupled with methylamine (16 μL, 2M in THF) under promotion of HATU (12 mg, 0.032 mmol) The title compound was obtained as solid (12 mg, 60%) after purification by flash chromatography, eluting with a gradient of 0-10% methanol in ethyl acetate. 1H NMR (400 MHz, CDCl3) δ 7.66 (d, J=7.1 Hz, 1H), 7.32-7.24 (m, 4H), 7.19-7.12 (m, 2H), 7.03-6.89 (m, 6H), 4.59 (br, 1H), 3.75 (s, 1H), 3.22 (br, 2H), 2.84 (d, J=4.9 Hz, 3H), 2.55 (s, 3H), 2.52-2.47 (m, 1H), 2.40-2.09 (m, 6H), 1.93-1.87 (m, 7H), 1.78-1.61 (m, 6H). HRMS m/z (M+H)+ calcd 612.3514, obsd 612.3530.

Quellen und Nachweise

ORD-Eintrag
ord-84e501dec7114380bc2b1d09c782b848
Quelldatensatz
uspto-grants-2010_01
Patentnummer
US07645771B2

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