5-Fluoropyridine-2-carboxaldehyde → 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((5-fluoropyridin-2-yl)methylamino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoic acid

HRID 85612

Reaktionsgleichung

Reaktionsgleichung von HRID 85612
[NH2:1][C@:2]12[CH2:37][CH2:36][C@@H:35]([C:38]([CH3:40])=[CH2:39])[C@@H:3]1[C@@H:4]1[C@@:17]([CH3:20])([CH2:18][CH2:19]2)[C@@:16]2([CH3:21])[C@@H:7]([C@:8]3([CH3:34])[C@@H:13]([CH2:14][CH2:15]2)[C:12]([CH3:23])([CH3:22])[C:11]([C:24]2[CH:33]=[CH:32][C:27]([C:28]([O:30]C)=[O:29])=[CH:26][CH:25]=2)=[CH:10][CH2:9]3)[CH2:6][CH2:5]1.FC1C=C(CN[C@]23CC[C@@H](C(C)=C)[C@@H]2[C@@H]2[C@@](C)(CC3)[C@@]3(C)[C@@H]([C@]4(C)[C@@H](CC3)C(C)(C)C(C3C=CC(C(O)=O)=CC=3)=CC4)CC2)C=CN=1.[F:88][C:89]1[CH:90]=[CH:91][C:92]([CH:95]=O)=[N:93][CH:94]=1>>[F:88][C:89]1[CH:90]=[CH:91][C:92]([CH2:95][NH:1][C@:2]23[CH2:37][CH2:36][C@@H:35]([C:38]([CH3:40])=[CH2:39])[C@@H:3]2[C@@H:4]2[C@@:17]([CH3:20])([CH2:18][CH2:19]3)[C@@:16]3([CH3:21])[C@@H:7]([C@:8]4([CH3:34])[C@@H:13]([CH2:14][CH2:15]3)[C:12]([CH3:23])([CH3:22])[C:11]([C:24]3[CH:33]=[CH:32][C:27]([C:28]([OH:30])=[O:29])=[CH:26][CH:25]=3)=[CH:10][CH2:9]4)[CH2:6][CH2:5]2)=[N:93][CH:94]=1

Komponenten

4

Edukt 3

HCID 103516975-Fluoropyridine-2-carboxaldehydeHCID 68357865methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-amino-1-isopropenyl-5a,5b,8,8,11a-pentamethyl-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoateHCID 683582074-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-fluoropyridin-4-yl)methylamino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoic acid

Produkt 1

HCID 683581344-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((5-fluoropyridin-2-yl)methylamino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoic acidAusbeute 47 %

Versuchsvorschrift

The title compound was prepared in 47% yield from methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-amino-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoate following the same procedure as described for the preparation of 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-fluoropyridin-4-yl)methylamino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoic acid, except 5-fluoro-2-formylpyridine was used instead of 2-fluoropyridine-4-carboxaldehyde in Step 1. LCMS: m/e 639.5 (M+H)+, 3.33 min (method 6). 1H NMR (500 MHz, 1:1 CDCl3:MeOD) δ=8.46 (d, J=2.7 Hz, 1H), 7.93 (d, J=8.2 Hz, 2H), 7.68 (dt, J=2.7, 8.2 Hz, 1H), 7.53 (dd, J=4.1, 8.7 Hz, 1H), 7.21 (d, J=8.5 Hz, 2H), 5.31 (dd, J=1.7, 6.3 Hz, 1H), 4.83 (s, 1H), 4.74 (s, 1H), 4.49 (d, J=15.3 Hz, 1H), 4.32 (d, J=15.0 Hz, 1H), 2.78 (dt, J=5.3, 10.9 Hz, 1H), 2.22-2.06 (m, 5H), 1.96 (dt, J=3.4, 12.2 Hz, 1H), 1.89-1.82 (m, 1H), 1.80 (d, J=10.7 Hz, 2H), 1.76 (s, 3H), 1.74-1.66 (m, 2H), 1.64-1.54 (m, 4H), 1.53-1.47 (m, 2H), 1.46-1.42 (m, 1H), 1.41-1.37 (m, 1H), 1.33 (s, 3H), 1.29 (dd, J=3.8, 9.9 Hz, 1H), 1.24 (dd, J=4.1, 13.0 Hz, 1H), 1.13 (s, 3H), 1.07 (s, 3H), 0.97 (s, 3H), 0.95 (s, 3H).

Aufarbeitung

  1. customm/e 639.5 (M+H)+, 3.33 min (method 6)

Quellen und Nachweise

ORD-Eintrag
ord-83c5780e797c4869992b5edc2b0b43cd
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08846647B2

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