Acetonitrile → 4-[[(3aS,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-[(E)-3-[[1-(4-chlorophenyl)cyclopropyl]amino]-3-oxo-prop-1-enyl]-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3H-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxo-butanoic acid

HRID 524447Notes

Reaction equation

HRID 524447 reaction equation
[CH3:1][C:2]([CH3:59])([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([CH3:56])[C@@H:28]2[CH2:27][CH2:26][C@H:25]2[C@@:20]3([CH3:55])[CH2:21][CH2:22][C@@:23]3(/[CH:40]=[CH:41]/[C:42]([NH:44][C:45]4([C:48]5[CH:53]=[CH:52][C:51]([Cl:54])=[CH:50][CH:49]=5)[CH2:47][CH2:46]4)=[O:43])[CH2:35][C:34](=[O:36])[C:33]([CH:37]([CH3:39])[CH3:38])=[C:24]32)[C:15]1([CH3:58])[CH3:57])=[O:12])[C:3]([O:5]C(C)(C)C)=[O:4].[C:60]([OH:66])([C:62]([F:65])([F:64])[F:63])=[O:61].CC#N>ClCCl>[C:60]([OH:66])([C:62]([F:65])([F:64])[F:63])=[O:61].[OH2:4].[Cl:54][C:51]1[CH:50]=[CH:49][C:48]([C:45]2([NH:44][C:42](=[O:43])/[CH:41]=[CH:40]/[C@:23]34[CH2:35][C:34](=[O:36])[C:33]([CH:37]([CH3:38])[CH3:39])=[C:24]3[C@@H:25]3[C@@:20]([CH3:55])([CH2:21][CH2:22]4)[C@@:19]4([CH3:56])[C@@H:28]([C@:29]5([CH3:32])[C@@H:16]([CH2:17][CH2:18]4)[C:15]([CH3:58])([CH3:57])[C@@H:14]([O:13][C:11](=[O:12])[CH2:10][C:2]([CH3:1])([CH3:59])[C:3]([OH:5])=[O:4])[CH2:31][CH2:30]5)[CH2:27][CH2:26]3)[CH2:47][CH2:46]2)=[CH:53][CH:52]=1

Participants

6

Reactant 3

HCID 6342AcetonitrileHCID 6422Trifluoroacetic acidHCID 896194261-tert-butyl 4-((3aS,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-((E)-3-((1-(4-chlorophenyl)cyclopropyl)amino)-3-oxoprop-1-en-1-yl)-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysen-9-yl) 2,2-dimethylsuccinate

Product 2

HCID 22392675Trifluoroacetic acid waterYield 0.05%HCID 865751644-[[(3aS,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-[(E)-3-[[1-(4-chlorophenyl)cyclopropyl]amino]-3-oxo-prop-1-enyl]-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3H-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxo-butanoic acidYield 58.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-tert-butyl 4-((3aS,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-((E)-3-((1-(4-chlorophenyl)cyclopropyl)amino)-3-oxoprop-1-en-1-yl)-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysen-9-yl) 2,2-dimethylsuccinate (460 mg, 0.554 mmol) in Dichloromethane (6 mL) was added TFA (3 mL, 0.554 mmol). The reaction mixture was stirred at r.t for 2 hs and evaporated in vacuo to afford crude product, which was purified by preparative-HPLC (Mobile Phase: A=0.05% TFA/H2O, B=MeCN) to give the product 4-(((3aS,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-((E)-3-((1-(4-chlorophenyl)cyclopropyl)amino)-3-oxoprop-1-en-1-yl)-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysen-9-yl)oxy)-2,2-dimethyl-4-oxobutanoic acid (130 mg, 0.162 mmol, 29.2%) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 9.00 (m, 1H), 7.31 (d, J=8.8 Hz, 2H), 7.15 (d, J=15.6 Hz, 1H), 7.06 (d, J=8.8 Hz, 2H), 5.99 (d, J=15.6 Hz, 1H), 4.56 (m, 1H), 3.11 (m, 1H), 2.89-0.80 (m, 54H); LC/MS: m/z calculated 773.4. Found 774.3 (M+1)+.

Workup

  1. customevaporated in vacuo
  2. customto afford crude product, which
  3. customwas purified by preparative-HPLC (Mobile Phase

Sources & evidence

ORD record
ord-175d76d2e32c4a1c82ee64abbd4bebc9
Source dataset
uspto-grants-2016_05
Patent number
US09340513B2

Reaction notes

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