Methanol → 4-(((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-((2-((1S,4S)-2,2-dioxido-2-thia-5-azabicyclo[2.2.1]heptan-5-yl)ethyl)amino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)-2,2-dimethyl-4-oxobutanoic acid

HRID 338669Notes

Reaction equation

HRID 338669 reaction equation
[CH3:1][C:2]([CH3:55])([CH2:10][C:11]([O:13][C@H:14]1[CH2:31][CH2:30][C@@:29]2([CH3:32])[C@@H:16]([CH2:17][CH2:18][C@:19]3([CH3:52])[C@@H:28]2[CH2:27][CH2:26][C@H:25]2[C@@:20]3([CH3:51])[CH2:21][CH2:22][C@@:23]3([NH:39][CH2:40][CH2:41][N:42]4[CH2:47][C@@H:46]5[CH2:48][C@H:43]4[CH2:44][S:45]5(=[O:50])=[O:49])[CH2:35][CH2:34][C@@H:33]([C:36]([CH3:38])=[CH2:37])[C@@H:24]32)[C:15]1([CH3:54])[CH3:53])=[O:12])[C:3]([O:5]C(C)(C)C)=[O:4].C(O)(C(F)(F)F)=O.CO>C(Cl)Cl.ClCCCl>[O:50]=[S:45]1(=[O:49])[CH2:44][C@@H:43]2[CH2:48][C@H:46]1[CH2:47][N:42]2[CH2:41][CH2:40][NH:39][C@:23]12[CH2:35][CH2:34][C@@H:33]([C:36]([CH3:38])=[CH2:37])[C@@H:24]1[C@@H:25]1[C@@:20]([CH3:51])([CH2:21][CH2:22]2)[C@@:19]2([CH3:52])[C@@H:28]([C@:29]3([CH3:32])[C@@H:16]([CH2:17][CH2:18]2)[C:15]([CH3:54])([CH3:53])[C@@H:14]([O:13][C:11](=[O:12])[CH2:10][C:2]([CH3:1])([CH3:55])[C:3]([OH:5])=[O:4])[CH2:31][CH2:30]3)[CH2:27][CH2:26]1

Participants

6

Reactant 3

HCID 887MethanolHCID 6422Trifluoroacetic acidHCID 1304732661-tert-butyl 4-((1R,3 aS,5aR,5bR,7aR,9S,11aR,11bR,13 aR,13bR)-3a-((2-((1S,4S)-2,2-dioxido-2-thia-5-azabicyclo[2.2.1]heptan-5-yl)ethyl)amino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yl) 2,2-dimethylsuccinate

Product 1

HCID 718162034-(((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-((2-((1S,4S)-2,2-dioxido-2-thia-5-azabicyclo[2.2.1]heptan-5-yl)ethyl)amino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)-2,2-dimethyl-4-oxobutanoic acidYield 18.8%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 1-tert-butyl 4-((1R,3 aS,5aR,5bR,7aR,9S,11aR,11bR,13 aR,13bR)-3a-((2-((1S,4S)-2,2-dioxido-2-thia-5-azabicyclo[2.2.1]heptan-5-yl)ethyl)amino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yl) 2,2-dimethylsuccinate (55.2 mg, 0.070 mmol) in DCM (1 mL) was added TFA (0.3 ml, 3.89 mmol). The reaction mixture was stirred rt and turned purple/red. After 1 h, TLC (95:5 DCM:MeOH) showed the reaction was completed. The reaction mixture was diluted with DCE (2 mL) and concentrated to a red solid. The crude material was redissolved in DCM (0.5 mL). Et2O was added to produce ad precipitate which was filtered and washed with Et2O to give 4-(((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-((2-((1S,4S)-2,2-dioxido-2-thia-5-azabicyclo[2.2.1]heptan-5-yl)ethyl)amino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)-2,2-dimethyl-4-oxobutanoic acid as off-white solid (9.5 mg, 18.8% yield). LC/MS: m/e 729.5 (M+H)+, 3.49 min (method 8). 1H NMR (400 MHz, CHLOROFORM-d) δ 4.79 (br. s., 1H), 4.68 (s, 1H), 4.54-4.43 (m, 1H), 4.23 (br. s., 1H), 3.58 (br. s., 1H), 3.49-3.31 (m, 2H), 3.29-3.13 (m, 3H), 3.11-2.91 (m, 4H), 2.79 (br. s., 1H), 2.72-2.64 (m, 1H), 2.59 (s, 1H), 2.56 (d, J=6.4 Hz, 1H), 2.39 (d, J=11.5 Hz, 1H), 2.28 (br. s., 1H), 1.93 (br. s., 4H), 1.70 (s, 3H), 1.69-1.49 (m, 9H), 1.48-1.40 (m, 3H), 1.35 (br. s., 2H), 1.31 (br. s., 3H), 1.30 (br. s., 3H), 1.09 (br. s., 3H), 1.03 (s, 3H), 1.00-0.89 (m, 2H), 0.86 (br. s., 3H), 0.85 (s, 3H), 0.83 (s, 3H), 0.79-0.73 (m, 1H)

Workup

  1. concentrationconcentrated to a red solid
  2. dissolutionThe crude material was redissolved in DCM (0.5 mL)
  3. additionEt2O was added
  4. customto produce ad precipitate which
  5. filtrationwas filtered
  6. washwashed with Et2O

Sources & evidence

ORD record
ord-7ecdba5f022e4dbd96c1191d8a9e61fe
Source dataset
uspto-grants-2014_11
Patent number
US08889854B2

Reaction notes

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