3-(Trifluoromethyl)pyridine-2-carboxaldehyde → 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-3a-((3-(trifluoromethyl)pyridin-2-yl)methylamino)-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 85613Notes

Reaction equation

HRID 85613 reaction equation
[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]([F:99])([F:98])[C:90]1[C:91]([CH:96]=O)=[N:92][CH:93]=[CH:94][CH:95]=1>>[CH3:20][C@:17]12[C@@:16]3([CH3:21])[C@@H:7]([C@:8]4([CH3:34])[C@@H:13]([CH2:14][CH2:15]3)[C:12]([CH3:22])([CH3:23])[C:11]([C:24]3[CH:25]=[CH:26][C:27]([C:28]([OH:30])=[O:29])=[CH:32][CH:33]=3)=[CH:10][CH2:9]4)[CH2:6][CH2:5][C@@H:4]1[C@H:3]1[C@H:35]([C:38]([CH3:40])=[CH2:39])[CH2:36][CH2:37][C@:2]1([NH:1][CH2:96][C:91]1[C:90]([C:89]([F:98])([F:88])[F:99])=[CH:95][CH:94]=[CH:93][N:92]=1)[CH2:19][CH2:18]2

Participants

4

Reactant 3

HCID 147614703-(Trifluoromethyl)pyridine-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

Product 1

HCID 683579194-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-3a-((3-(trifluoromethyl)pyridin-2-yl)methylamino)-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 acidYield 42%

Procedure

The title compound was prepared in 42% 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 3-trifluoromethylpyridine-2-carbaldehyde was used instead of 2-fluoropyridine-4-carboxaldehyde in Step 1. LCMS: m/e 689.6 (M+H)+, 4.12 min (method 6). 1H NMR (500 MHz, 1:1 CDCl3:MeOD) δ=8.83 (d, J=4.3 Hz, 1H), 8.28 (d, J=7.9 Hz, 1H), 7.93 (d, J=8.5 Hz, 2H), 7.72 (dd, J=5.0, 7.8 Hz, 1H), 7.21 (d, J=8.5 Hz, 2H), 5.31 (dd, J=1.5, 6.1 Hz, 1H), 4.85 (s, 1H), 4.76 (s, 1H), 4.44 (d, J=16.2 Hz, 1H), 2.80 (dt, J=5.5, 11.0 Hz, 1H), 2.25-2.10 (m, 5H), 2.02 (dt, J=3.5, 12.1 Hz, 1H), 1.92-1.79 (m, 2H), 1.78 (s, 3H), 1.76-1.68 (m, 3H), 1.64-1.54 (m, 4H), 1.52-1.43 (m, 3H), 1.40 (br. s., 1H), 1.36 (s, 3H), 1.32-1.22 (m, 2H), 1.16-1.13 (m, 3H), 1.08 (s, 3H), 0.97 (s, 3H), 0.95 (s, 3H).

Workup

  1. customm/e 689.6 (M+H)+, 4.12 min (method 6)

Sources & evidence

ORD record
ord-80a5a63c53ac4cd292994dbef15b9be6
Source dataset
uspto-grants-2014_09
Patent number
US08846647B2

Reaction notes

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