Diisopropylethylamine → tert-butyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((3-tert-butoxy-N-(2-(dimethylamino)ethyl)-3-oxopropanamido)methyl)-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

HRID 405070Notes

Reaction equation

HRID 405070 reaction equation
[CH3:1][N:2]([CH3:49])[CH2:3][CH2:4][NH:5][CH2:6][C@:7]12[CH2:45][CH2:44][C@@H:43]([C:46]([CH3:48])=[CH2:47])[C@@H:8]1[C@@H:9]1[C@@:22]([CH3:25])([CH2:23][CH2:24]2)[C@@:21]2([CH3:26])[C@@H:12]([C@:13]3([CH3:42])[C@@H:18]([CH2:19][CH2:20]2)[C:17]([CH3:28])([CH3:27])[C:16]([C:29]2[CH:41]=[CH:40][C:32]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])=[CH:31][CH:30]=2)=[CH:15][CH2:14]3)[CH2:11][CH2:10]1.CCN(C(C)C)C(C)C.[C:59]([O:65][C:66]([CH3:69])([CH3:68])[CH3:67])(=[O:64])[CH2:60][C:61]([O-])=[O:62].F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1>ClCCCl.CN(C1C=CN=CC=1)C>[C:66]([O:65][C:59](=[O:64])[CH2:60][C:61]([N:5]([CH2:6][C@:7]12[CH2:45][CH2:44][C@@H:43]([C:46]([CH3:48])=[CH2:47])[C@@H:8]1[C@@H:9]1[C@@:22]([CH3:25])([CH2:23][CH2:24]2)[C@@:21]2([CH3:26])[C@@H:12]([C@:13]3([CH3:42])[C@@H:18]([CH2:19][CH2:20]2)[C:17]([CH3:28])([CH3:27])[C:16]([C:29]2[CH:41]=[CH:40][C:32]([C:33]([O:35][C:36]([CH3:37])([CH3:38])[CH3:39])=[O:34])=[CH:31][CH:30]=2)=[CH:15][CH2:14]3)[CH2:11][CH2:10]1)[CH2:4][CH2:3][N:2]([CH3:1])[CH3:49])=[O:62])([CH3:69])([CH3:68])[CH3:67]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 21883978Tert-butyl malonateHCID 86676399tert-butyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-(dimethylamino)ethylamino)methyl)-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

Product 1

HCID 86676409tert-butyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((3-tert-butoxy-N-(2-(dimethylamino)ethyl)-3-oxopropanamido)methyl)-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)benzoateYield 97.5%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 111,2-DichloroethaneSolvent

Procedure

To a solution of tert-butyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-(dimethylamino)ethylamino)methyl)-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 (27 mg, 0.040 mmol) in DCE (2 ml) was added Hunig's base (0.021 ml, 0.121 mmol), DMAP (1 mg, 8.19 μmol), Mono-tert-butyl malonate (0.012 ml, 0.080 mmol), and O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium tetrafluoroborate (19.38 mg, 0.060 mmol). The mixture was stirred at rt. After 5 h of stirring, the mixture was loaded directly onto a silica gel column and was purified using a 0-5% MeOH in dichloromethane gradient to afford tert-butyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((3-tert-butoxy-N-(2-(dimethylamino)ethyl)-3-oxopropanamido)methyl)-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 as a white foam (31.8 mg, 0.039 mmol, 97% yield). LCMS: m/e 813.4 (M−H)−, 3.46 min (method 6).

Workup

  1. stirringAfter 5 h of stirring
  2. customwas purified

Sources & evidence

ORD record
ord-bd6f643eee8c4db4bb2b6092d13845f4
Source dataset
uspto-grants-2014_06
Patent number
US08748415B2

Reaction notes

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