3-Amino-1-(pyrrolidin-1-yl)propan-1-one hydrochloride → 4-[(1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-1-isopropenyl-5a,5b,8,8,11a-pentamethyl-3a-[[(3-oxo-3-pyrrolidin-1-yl-propyl)amino]methyl]-1,2,3,4,5,6,7,7a,11,11b,12,13,13a,13b-tetradecahydrocyclopenta[a]chrysen-9-yl]-2-fluoro-benzoic acid

HRID 405080Notes

Reaction equation

HRID 405080 reaction equation
[F:1][C:2]1[CH:11]=[C:10]([C:12]2[C:13]([CH3:42])([CH3:41])[C@H:14]3[C@:27]([CH3:30])([CH2:28][CH:29]=2)[C@@H:26]2[C@:17]([CH3:40])([C@@:18]4([CH3:39])[C@H:23]([CH2:24][CH2:25]2)[C@H:22]2[C@H:31]([C:34]([CH3:36])=[CH2:35])[CH2:32][CH2:33][C@:21]2([CH:37]=O)[CH2:20][CH2:19]4)[CH2:16][CH2:15]3)[CH:9]=[CH:8][C:3]=1[C:4]([O:6]C)=[O:5].Cl.[NH2:44][CH2:45][CH2:46][C:47]([N:49]1[CH2:53][CH2:52][CH2:51][CH2:50]1)=[O:48]>>[F:1][C:2]1[CH:11]=[C:10]([C:12]2[C:13]([CH3:42])([CH3:41])[C@H:14]3[C@:27]([CH3:30])([CH2:28][CH:29]=2)[C@@H:26]2[C@:17]([CH3:40])([C@@:18]4([CH3:39])[C@H:23]([CH2:24][CH2:25]2)[C@H:22]2[C@H:31]([C:34]([CH3:36])=[CH2:35])[CH2:32][CH2:33][C@:21]2([CH2:37][NH:44][CH2:45][CH2:46][C:47](=[O:48])[N:49]2[CH2:53][CH2:52][CH2:51][CH2:50]2)[CH2:20][CH2:19]4)[CH2:16][CH2:15]3)[CH:9]=[CH:8][C:3]=1[C:4]([OH:6])=[O:5]

Participants

3

Reactant 2

HCID 219492223-Amino-1-(pyrrolidin-1-yl)propan-1-one hydrochlorideHCID 86676413methyl 2-fluoro-4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-formyl-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

Product 1

HCID 601526214-[(1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-1-isopropenyl-5a,5b,8,8,11a-pentamethyl-3a-[[(3-oxo-3-pyrrolidin-1-yl-propyl)amino]methyl]-1,2,3,4,5,6,7,7a,11,11b,12,13,13a,13b-tetradecahydrocyclopenta[a]chrysen-9-yl]-2-fluoro-benzoic acidYield 67%

Procedure

The title compound was prepared in 67% yield following steps 5 and 6, using methyl 2-fluoro-4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-formyl-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 and 3-amino-1-(pyrrolidin-1-yl)propan-1-one hydrochloride as the reactant amine MS: m/e 687.5 (MH+), 1.74 min (method 2). 1H NMR (400 MHz, MeOD) δ ppm 0.96 (s, 3H) 0.98 (s, 3H) 1.02 (s, 3H) 1.08 (s, 3H) 1.16 (s, 3H) 1.73 (s, 3H) 0.90-1.86 (m, 20H) 1.88-1.96 (m, J=6.78, 6.78, 6.65, 6.40 Hz, 2H) 1.97-2.10 (m, 1H) 2.01 (dt, J=13.74, 6.81 Hz, 2H) 2.16 (dd, J=17.19, 6.40 Hz, 1H) 2.47-2.57 (m, 1H) 2.81 (t, J=6.02 Hz, 2H) 2.88 (d, J=12.55 Hz, 1H) 3.33-3.42 (m, 3H) 3.42-3.52 (m, 4H) 4.65 (s, 1H) 4.76 (d, J=1.76 Hz, 1H) 5.35 (dd, J=5.77, 1.00 Hz, 1H) 6.94 (d, J=11.80 Hz, 1H) 7.02 (dd, J=8.03, 1.25 Hz, 1H) 7.83 (t, J=7.91 Hz, 1H). 19F NMR (376 MHz, MeOD) δ ppm −112.76 (s, 1 F).

Workup

  1. customm/e 687.5 (MH+), 1.74 min (method 2)

Sources & evidence

ORD record
ord-52e35b1ad5b34953a3d53e18080233f3
Source dataset
uspto-grants-2014_06
Patent number
US08748415B2

Reaction notes

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