Hydrochloric Acid → (E)-N-(1-(4-chlorophenyl)cyclopropyl)-3-((3aS,5aR,5bR,7aR,9S,11aR,11bR,13aS)-9-hydroxy-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-3a-yl)-2-methylacrylamide

HRID 524469Notes

Reaction equation

HRID 524469 reaction equation
[OH:1][C@H:2]1[CH2:19][CH2:18][C@@:17]2([CH3:20])[C@@H:4]([CH2:5][CH2:6][C@:7]3([CH3:35])[C@@H:16]2[CH2:15][CH2:14][C@H:13]2[C@@:8]3([CH3:34])[CH2:9][CH2:10][C@@:11]3(/[CH:28]=[C:29](\[CH3:33])/[C:30](O)=[O:31])[CH2:23][C:22](=[O:24])[C:21]([CH:25]([CH3:27])[CH3:26])=[C:12]32)[C:3]1([CH3:37])[CH3:36].Cl.[Cl:39][C:40]1[CH:45]=[CH:44][C:43]([C:46]2([NH2:49])[CH2:48][CH2:47]2)=[CH:42][CH:41]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.Cl>CN(C=O)C>[Cl:39][C:40]1[CH:41]=[CH:42][C:43]([C:46]2([NH:49][C:30](=[O:31])/[C:29](/[CH3:33])=[CH:28]/[C@:11]34[CH2:23][C:22](=[O:24])[C:21]([CH:25]([CH3:26])[CH3:27])=[C:12]3[C@@H:13]3[C@@:8]([CH3:34])([CH2:9][CH2:10]4)[C@@:7]4([CH3:35])[C@@H:16]([C@:17]5([CH3:20])[C@@H:4]([CH2:5][CH2:6]4)[C:3]([CH3:37])([CH3:36])[C@@H:2]([OH:1])[CH2:19][CH2:18]5)[CH2:15][CH2:14]3)[CH2:47][CH2:48]2)=[CH:44][CH:45]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 242065841-(4-Chlorophenyl)cyclopropanamine hydrochlorideHCID 89661749(E)-3-((3aS,5aR,5bR,7aR,9S,11aR,11bR,13aS)-9-hydroxy-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-3a-yl)-2-methylacrylic acid

Product 1

HCID 117701483(E)-N-(1-(4-chlorophenyl)cyclopropyl)-3-((3aS,5aR,5bR,7aR,9S,11aR,11bR,13aS)-9-hydroxy-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-3a-yl)-2-methylacrylamideYield 99.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
20 °C

Procedure

To a solution of (E)-3-((3aS,5aR,5bR,7aR,9S,11aR,11bR,13aS)-9-hydroxy-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-3a-yl)-2-methylacrylic acid (350 mg, 0.685 mmol), 1-(4-chlorophenyl)cyclopropanamine hydrochloride (154 mg, 0.754 mmol) and HATU (521 mg, 1.371 mmol) in DMF (2 mL) stirred at 0° C. was added DIPEA (0.479 mL, 2.74 mmol). The reaction mixture was stirred at 20° C. for 1 h. The reaction mixture was pH adjusted to 3-4 with 2 M HCl and filtered. The solid was washed with water (50 mL), dissolved into DCM, dried over sodium sulfate and evaporated in vacuo to give the crude (E)-N-(1-(4-chlorophenyl)cyclopropyl)-3-((3aS,5aR,5bR,7aR,9S,11aR,11bR,13aS)-9-hydroxy-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-3a-yl)-2-methylacrylamide (650 mg, 0.680 mmol, 99%) as a yellow solid.

Workup

  1. filtrationfiltered
  2. washThe solid was washed with water (50 mL)
  3. dissolutiondissolved into DCM
  4. dry with materialdried over sodium sulfate
  5. customevaporated in vacuo

Sources & evidence

ORD record
ord-7895dfcd6bc84b0782c177098335d3b1
Source dataset
uspto-grants-2016_05
Patent number
US09340513B2

Reaction notes

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