1,2-Dichloroethane → HCID 90353805, compound

HRID 1773032Notes

Reaction equation

HRID 1773032 reaction equation
[O:1]=[S:2]1(=[O:49])[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][NH:10][C@:11]23[CH2:45][CH2:44][C@@H:43]([C:46]([CH3:48])=[CH2:47])[C@@H:12]2[C@@H:13]2[C@@:26]([CH3:29])([CH2:27][CH2:28]3)[C@@:25]3([CH3:30])[C@@H:16]([C@:17]4([CH3:42])[C@@H:22]([CH2:23][CH2:24]3)[C:21]([CH3:32])([CH3:31])[C:20]([CH2:33][CH2:34][C:35]([CH3:41])([CH3:40])[CH2:36][C:37](O)=[O:38])=[CH:19][CH2:18]4)[CH2:15][CH2:14]2)[CH2:4][CH2:3]1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.C(N(CC)C(C)C)(C)C.[N:73]#[C:74][NH2:75]>CN(C=O)C>[C:74]([NH:75][C:37](=[O:38])[CH2:36][C:35]([CH3:41])([CH3:40])[CH2:34][CH2:33][C:20]1[C:21]([CH3:32])([CH3:31])[C@H:22]2[C@:17]([CH3:42])([CH2:18][CH:19]=1)[C@@H:16]1[C@:25]([CH3:30])([C@@:26]3([CH3:29])[C@H:13]([CH2:14][CH2:15]1)[C@H:12]1[C@H:43]([C:46]([CH3:48])=[CH2:47])[CH2:44][CH2:45][C@:11]1([NH:10][CH2:9][CH2:8][N:5]1[CH2:4][CH2:3][S:2](=[O:49])(=[O:1])[CH2:7][CH2:6]1)[CH2:28][CH2:27]3)[CH2:24][CH2:23]2)#[N:73]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 9864CyanamideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 78320688HCID 78320688, compound

Product 1

HCID 90353805HCID 90353805, compoundYield 28.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 5-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-(1,1-dioxidothiomorpholino)ethyl)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)-3,3-dimethylpentanoic acid (30 mg, 0.043 mmol) in DMF (1 mL) was treated with EDC (11.7 mg, 0.061 mmol) and HOBT (8.2 mg, 0.053 mmol). The reaction mixture was stirred at rt for 1 h. N,N-diisopropylethylamine (0.013 mL, 0.073 mmol) was added to the reaction mixture and after stirring 10 min, cyanamide (1.0 mg, 0.024 mmol) was then added. The reaction mixture was stirred at room temperature for 16 h. The mixture was concentrated and the crude product was purified by prep HPLC (Method 12) to afford N-cyano-5-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-(1,1-dioxidothiomorpholino)ethyl)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)-3,3-dimethylpentanamide (4.9 mg, 28% yield). LC/MS m/e 723.5 (M+H)+, 2.29 min (method 3). 1H NMR (500 MHz, DMSO-d6) δ 5.19 (d, J=5.9 Hz, 1H), 4.71 (s, 1H), 4.58 (s, 1H), 3.49 (t, J=4.8 Hz, 1H), 3.42 (t, J=5.5 Hz, 1H), 3.14-3.03 (m, 4H), 3.01-2.92 (m, 4H), 2.72-2.58 (m, 3H), 1.96-0.76 (m, 28H), 1.66 (s, 3H), 1.04 (s, 3H), 0.95 (s, 6H), 0.92 (s, 6H), 0.87 (s, 3H), 0.79 (s, 3H)

Workup

  1. stirringafter stirring 10 min
  2. stirringThe reaction mixture was stirred at room temperature for 16 h
  3. concentrationThe mixture was concentrated
  4. customthe crude product was purified by prep HPLC (Method 12)

Sources & evidence

ORD record
ord-1b76c478b9a1423b959e8fb6737eaf84
Source dataset
uspto-grants-2016_02
Patent number
US09249180B2

Reaction notes

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