Tetrahydrofuran → HCID 45102225, compound

HRID 1039141Notes

Reaction equation

HRID 1039141 reaction equation
[CH2:1]([C@@:8]12[CH2:21][C:20](=[O:22])[C@:19]([OH:29])([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH2:18][C@H:17]1[CH2:16][CH2:15][C:14]1[CH:13]=[C:12]([C:30]([NH:32][C:33]3[C:34]([CH3:39])=[N:35][CH:36]=[CH:37][CH:38]=3)=[O:31])[CH:11]=[CH:10][C:9]2=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:40]1COCC1.[Li]C.[NH4+].[Cl-]>C(#N)C.O>[CH2:1]([C@@:8]12[CH2:21][C@:20]([OH:22])([CH3:40])[C@:19]([OH:29])([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH2:18][C@H:17]1[CH2:16][CH2:15][C:14]1[CH:13]=[C:12]([C:30]([NH:32][C:33]3[C:34]([CH3:39])=[N:35][CH:36]=[CH:37][CH:38]=3)=[O:31])[CH:11]=[CH:10][C:9]2=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 25517Ammonium ChlorideHCID 59243446(4bR,7R,8aR)-4b-benzyl-7-hydroxy-N-(2-methylpyridin-3-yl)-6-oxo-7-phenyl-4b,5,6,7,8,8a,9,10-octahydrophenanthrene-2-carboxamideHCID 178418348HCID 178418348, compound

Product 1

HCID 45102225HCID 45102225, compoundYield 73%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
-17 °C

Procedure

To a flame dried 50 mL round bottom flask was added the (4bR,7R,8aR)-4b-benzyl-7-hydroxy-N-(2-methylpyridin-3-yl)-6-oxo-7-phenyl-4b,5,6,7,8,8a,9,10-octahydrophenanthrene-2-carboxamide (0.28 g, 0.54 mmol) in a THF (5 mL). The solution was cooled to −17° C. in an ice/acetone bath. To the reaction was added MeLi*LiBr (0.1 mL). After 1 hour the LCMS indicated that starting material remained so an additional 0.15 mL was added. The reaction stirred to room temperature over 2 hours. By HPLC, 2.5% of the starting material remained. To the reaction was added NH4Cl slowly and off gassing was observed. The reaction was diluted to 125 mL with acetonitrile and water. The reaction was purified by reverse phase chromatography then was lyophilized. The resulting dried powder was dissolved in acetonitrile and water again with two drops of concentrated HCl. The solution was lyophilized to dryness. This afforded the title product (231.4 mg) as the HCl salt in 73% yield. LRMS ES+ 533.1 1H NMR (300 MHz, METHANOL-d4) δ ppm 1.23-1.28 (m, 3 H) 1.53-1.62 (m, 1 H) 1.90-2.20 (m, 3 H) 2.70-2.74 (m, 3 H) 2.84 (d, J=14.90 Hz, 1 H) 2.92-3.22 (m, 2 H) 3.28-3.40 (m, 4 H) 3.91 (d, J=12.08 Hz, 1 H) 6.50 (d, J=8.26 Hz, 2 H) 6.84-6.92 (m, 2 H) 6.99-7.10 (m, 3 H) 7.13-7.29 (m, 3 H) 7.45 (dd, J=8.15, 1.91 Hz, 1 H) 7.56-7.65 (m, 2 H) 7.77 (d, J=1.81 Hz, 1 H) 7.88 (dd, J=8.26, 5.84 Hz, 1 H) 8.51-8.63 (m, 2 H).

Workup

  1. customTo a flame dried 50 mL round bottom flask
  2. additionwas added
  3. customThe reaction was purified by reverse phase chromatography
  4. customThe resulting dried powder
  5. dissolutionwas dissolved in acetonitrile

Sources & evidence

ORD record
ord-42f447f25c7947e6b6531cf6322f498f
Source dataset
uspto-grants-2013_10
Patent number
US08552035B2

Reaction notes

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