methyl 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)benzoate → 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(2-(3,3-difluoropyrrolidin-1-yl)acetamido)-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 85597Notes

Reaction equation

HRID 85597 reaction equation
N[C@]12CC[C@@H](C(C)=C)[C@@H]1[C@@H]1[C@@](C)(CC2)[C@@]2(C)[C@@H]([C@]3(C)[C@@H](CC2)C(C)(C)C(C2C=CC(C(OC)=O)=CC=2)=CC3)CC1.[F:41][C:42]1([F:90])[CH2:47][CH2:46][N:45]([CH2:48][C:49]([NH:51][C@:52]23[CH2:86][CH2:85][C@@H:84]([C:87]([CH3:89])=[CH2:88])[C@@H:53]2[C@@H:54]2[C@@:67]([CH3:70])([CH2:68][CH2:69]3)[C@@:66]3([CH3:71])[C@@H:57]([C@:58]4([CH3:83])[C@@H:63]([CH2:64][CH2:65]3)[C:62]([CH3:73])([CH3:72])[C:61]([C:74]3[CH:82]=[CH:81][C:77]([C:78]([OH:80])=[O:79])=[CH:76][CH:75]=3)=[CH:60][CH2:59]4)[CH2:56][CH2:55]2)=[O:50])C[CH2:43]1>>[F:41][C:42]1([F:90])[CH2:47][CH2:46][N:45]([CH2:48][C:49]([NH:51][C@:52]23[CH2:86][CH2:85][C@@H:84]([C:87]([CH3:89])=[CH2:88])[C@@H:53]2[C@@H:54]2[C@@:67]([CH3:70])([CH2:68][CH2:69]3)[C@@:66]3([CH3:71])[C@@H:57]([C@:58]4([CH3:83])[C@@H:63]([CH2:64][CH2:65]3)[C:62]([CH3:73])([CH3:72])[C:61]([C:74]3[CH:82]=[CH:81][C:77]([C:78]([OH:80])=[O:79])=[CH:76][CH:75]=3)=[CH:60][CH2:59]4)[CH2:56][CH2:55]2)=[O:50])[CH2:43]1

Participants

3

Reactant 2

HCID 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 683580394-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(2-(4,4-difluoropiperidin-1-yl)acetamido)-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 683580834-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(2-(3,3-difluoropyrrolidin-1-yl)acetamido)-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 acidYield 38%

Procedure

The title compound was prepared in 38% 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-(4,4-difluoropiperidin-1-yl)acetamido)-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 and 3,3-difluoropyrrolidine, HCl was used instead of 4,4-difluoropiperidine, HCl in Step 2. LCMS: m/e 677.5 (M+H)+, 2.26 min (method 6). 1H NMR (500 MHz, 1:1 CDCl3:MeOD) δ=7.92 (d, J=8.2 Hz, 2H), 7.40 (s, 1H), 7.20 (d, J=8.2 Hz, 2H), 5.29 (dd, J=1.7, 6.3 Hz, 1H), 4.75 (d, J=1.2 Hz, 1H), 4.65 (s, 1H), 3.59-3.44 (m, 2H), 3.43-3.36 (m, 1H), 3.31-3.20 (m, 2H), 2.63-2.55 (m, 1H), 2.55-2.47 (m, 3H), 2.47-2.39 (m, 1H), 2.13 (dd, J=6.4, 17.1 Hz, 1H), 1.94-1.83 (m, 1H), 1.81-1.76 (m, 2H), 1.76-1.73 (m, 1H), 1.72 (s, 3H), 1.70-1.65 (m, 1H), 1.57-1.46 (m, 6H), 1.46-1.40 (m, 2H), 1.39-1.31 (m, 2H), 1.26 (dd, J=2.7, 10.7 Hz, 1H), 1.19-1.10 (m, 2H), 1.09 (s, 3H), 1.03 (s, 3H), 1.02 (s, 3H), 0.95 (s, 3H), 0.94 (s, 3H).

Workup

  1. customm/e 677.5 (M+H)+, 2.26 min (method 6)

Sources & evidence

ORD record
ord-7ad31e7b3c954cfbbaa5f54c0a27434c
Source dataset
uspto-grants-2014_09
Patent number
US08846647B2

Reaction notes

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