Benzimidazole → HCID 11305671, compound

HRID 254183Notes

Reaction equation

HRID 254183 reaction equation
[C:1]([O:4][C@H:5]1[CH2:22][CH2:21][C@@:20]2([CH3:23])[C:7](=[CH:8][CH2:9][C@@H:10]3[C@@H:19]2[CH2:18][CH2:17][C@@:15]2([CH3:16])[C@H:11]3[CH2:12][C:13]([CH:25]=[O:26])=[C:14]2Cl)[CH2:6]1)(=[O:3])[CH3:2].[N:27]1[C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=2[NH:29][CH:28]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[C:1]([O:4][C@H:5]1[CH2:22][CH2:21][C@@:20]2([CH3:23])[C:7](=[CH:8][CH2:9][C@@H:10]3[C@@H:19]2[CH2:18][CH2:17][C@@:15]2([CH3:16])[C@H:11]3[CH2:12][C:13]([CH:25]=[O:26])=[C:14]2[N:27]2[C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=3[N:29]=[CH:28]2)[CH2:6]1)(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 5798BenzimidazoleHCID 11430Potassium CarbonateHCID 1047470117-Chloro-16-formylandrosta-5,16-dien-3beta-yl acetate

Product 1

HCID 11305671HCID 11305671, compoundYield 88.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 3β-Acetoxy-17-chloro-16-formylandrosta-5,16-diene (2, 2.5 g, 6.65 mmol), benzimidazole (2.35 g, 19.9 mmol), and K2CO3 (2.76 g, 23.9 mmol) in dry DMF (20 mL) is stirred at ca. 80° C. under Ar for 1.5 h. After cooling to room temperature, the reaction mixture is poured onto ice-cold water (250 mL) and the resulting precipitate is filtered, washed with water, and dried to give a crude dirty white solid (ca. 2.9 g). Purification by FCC [petroleum ether/EtOAc/Et3N (6:4:0.3)] gives 2.7 g (88.7%) of pure compound 3: mp 227-230° C.; IR (CHCl3) 3691, 3024, 2951, 2359, 1725, 1670, 1604, 1491, 1452, 1375, 1253, 1032, 897, 852, 818, 700, 657, 618, 576, 565, 550, 529, 511, 476 cm−1; 1H NMR (300 MHz, CDCl3) δ 1.07 (s, 6H, 18- and 19-CH3), 2.04 (s, 3H, 3β-OCH3), 4.60 (m, 1H, 3α-H), 5.43 (br s, 1H, 6-H), 7.35 (br. s, 2H, aromatic-Hs), 7.85 (s, 1H, aromatic-H), 7.98 (s, 1H, aromatic-H), 7.98 (s, 1H-21-H) and 9.59 (s, 1H, 16-CHO). HRMS calcd 481.2462 (C29H34O3N2.Na+). found 481.2454.

Workup

  1. temperatureAfter cooling to room temperature
  2. additionthe reaction mixture is poured onto ice-cold water (250 mL)
  3. filtrationthe resulting precipitate is filtered
  4. washwashed with water
  5. customdried
  6. customto give a crude dirty white solid (ca. 2.9 g)
  7. customPurification by FCC [petroleum ether/EtOAc/Et3N (6:4:0.3)]

Sources & evidence

ORD record
ord-75356a48466f42e6bb7fd83f7ae0e9a8
Source dataset
uspto-grants-2011_01
Patent number
US07875599B2

Reaction notes

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