[4-(Propan-2-yl)piperazin-1-yl]acetic acid → 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(2-(4-isopropylpiperazin-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 85585Notes

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.CN(C)CCC(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(O)=O)=CC=2)=CC3)CC1)=O.[CH:87]([N:90]1[CH2:95][CH2:94][N:93]([CH2:96][C:97]([OH:99])=O)[CH2:92][CH2:91]1)([CH3:89])[CH3:88]>>[CH:87]([N:90]1[CH2:91][CH2:92][N:93]([CH2:96][C:97]([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: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]2)=[O:99])[CH2:94][CH2:95]1)([CH3:88])[CH3:89]

Participants

Reactant 3

HCID 2759512[4-(Propan-2-yl)piperazin-1-yl]acetic acid

HCID 683578604-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(3-(dimethylamino)propanamido)-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

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)benzoate

Product 1

HCID 601519614-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(2-(4-isopropylpiperazin-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 22%

Procedure

The title compound was prepared in 22% 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-(3-(dimethylamino)propanamido)-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 (4-isopropyl-piperazin-1-yl)-acetic acid was used instead of 3-(dimethylamino)propionic acid hydrochloride in Step 1. LCMS: m/e 698.6 (M+H)+, 2.64 min (method 6). 1H NMR (500 MHz, 1:1 CDCl3:MeOD) δ=7.92 (d, J=8.2 Hz, 2H), 7.37 (br. s., 1H), 7.20 (d, J=8.2 Hz, 2H), 6.34-6.03 (m, 1H), 5.29 (d, J=4.6 Hz, 1H), 4.76 (br. s., 1H), 4.70 (br. s., 1H), 3.95 (br. s., 1H), 3.84-3.55 (m, 8H), 3.17 (q, J=7.2 Hz, 2H), 2.64 (d, J=13.1 Hz, 2H), 2.39 (dd, J=8.1, 11.4 Hz, 1H), 2.12 (dd, J=6.3, 17.2 Hz, 1H), 1.96-1.84 (m, 2H), 1.79 (d, J=12.5 Hz, 1H), 1.76-1.65 (m, 5H), 1.59-1.40 (m, 14H), 1.35 (t, J=7.2 Hz, 4H), 1.29-1.21 (m, 1H), 1.15 (d, J=6.1 Hz, 1H), 1.10 (br. s., 3H), 1.02 (s, 3H), 1.01 (br. s., 2H), 0.94 (br. s., 3H), 0.93 (br. s., 3H).

Workup

customm/e 698.6 (M+H)+, 2.64 min (method 6)

Sources & evidence

ORD record: ord-2d30451112814ed2ba977840760229eb
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08846647B2

Reaction notes

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