2-(Thiophene-2-sulfonamido)acetic acid → 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-3a-(2-(thiophene-2-sulfonamido)acetamido)-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 85596Notes

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.[S:87]1[CH:91]=[CH:90][CH:89]=[C:88]1[S:92]([NH:95][CH2:96][C:97](O)=[O:98])(=[O:94])=[O:93]>>[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: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][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][C:97](=[O:98])[CH2:96][NH:95][S:92]([C:88]1[S:87][CH:91]=[CH:90][CH:89]=1)(=[O:93])=[O:94])[CH2:19][CH2:18]2

Participants

Reactant 3

HCID 31550632-(Thiophene-2-sulfonamido)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 683582034-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-3a-(2-(thiophene-2-sulfonamido)acetamido)-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 31%

Procedure

The title compound was prepared in 31% 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 2-(thiophene-2-sulfonamido)acetic acid was used instead of 3-(dimethylamino)propionic acid hydrochloride in Step 1. LCMS: m/e 733.6 (M+H)+, 2.06 min (method 6). 1H NMR (500 MHz, 1:1 CDCl3:MeOD) δ=7.92 (d, J=8.5 Hz, 2H), 7.73 (dd, J=1.4, 5.0 Hz, 1H), 7.66 (dd, J=1.2, 3.7 Hz, 1H), 7.20 (d, J=8.2 Hz, 2H), 7.16 (dd, J=3.8, 5.0 Hz, 1H), 6.88 (s, 1H), 5.32-5.26 (m, 1H), 4.78 (d, J=1.5 Hz, 1H), 3.58-3.45 (m, 2H), 2.63-2.57 (m, 1H), 2.56-2.50 (m, 1H), 2.42 (dd, J=8.2, 12.2 Hz, 1H), 2.13 (dd, J=6.3, 17.2 Hz, 1H), 1.98-1.88 (m, 1H), 1.87-1.76 (m, 2H), 1.73 (br. s., 1H), 1.72 (s, 3H), 1.70-1.66 (m, 1H), 1.63-1.53 (m, 3H), 1.53-1.46 (m, 4H), 1.45-1.37 (m, 3H), 1.37-1.30 (m, 2H), 1.28-1.22 (m, 1H), 1.14 (s, 3H), 1.10 (d, J=3.1 Hz, 1H), 1.03 (s, 3H), 1.02 (s, 3H), 0.94 (s, 3H), 0.94 (br. s., 3H).

Workup

customm/e 733.6 (M+H)+, 2.06 min (method 6)

Sources & evidence

ORD record: ord-8a9056ce3efe4df294729247e6f646fa
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08846647B2

Reaction notes

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