Tetrahydrofuran → HCID 69846031, compound

HRID 1836618Notes

Reaction equation

HRID 1836618 reaction equation
C[Mg]Br.[C:4]([C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[N:11]([S:15]([C:18]1[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][CH:19]=1)(=[O:17])=[O:16])[CH:10]=[C:9]2[C@@H:25]1[CH2:27][C@H:26]1[C:28](N(OC)C)=[O:29])#[N:5].[CH2:34]1COCC1>C(OCC)C>[C:28]([C@@H:26]1[CH2:27][C@H:25]1[C:9]1[C:8]2[C:12](=[CH:13][CH:14]=[C:6]([C:4]#[N:5])[CH:7]=2)[N:11]([S:15]([C:18]2[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][CH:19]=2)(=[O:16])=[O:17])[CH:10]=1)(=[O:29])[CH3:34]

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 88019557HCID 88019557, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 69846031HCID 69846031, compoundYield 58%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
0 °C

Procedure

A solution of methylmagnesium bromide (3.0 M in diethyl ether, 0.826 ml, 2.48 mmol, 1.05 equiv) was added to a suspension of [trans-2-[5-cyano-1-(p-toluenesulfonyl)indol-3-yl]cycloprop-1-yl]-N-methoxy-N-methylcarboxamide (1 g, 2.36 mmol) in anhydrous diethyl ether (25 ml). The resulting mixture was stirred at 0° C. for 2 h. The reaction mixture was diluted anhydrous THF (15 ml) and stirred for an additional 3 h at 0° C. The cold mixture was quenched with aqueous 1 M hydrochloric acid (200 ml) and extracted with ethyl acetate (3×100 ml). The combined organic extracts were washed with brine (50 ml), dried over anhydrous magnesium sulfate, filtered, and concentrated. The crude reaction mixture was purified by silica gel column chromatography using a step gradient [2:1, 1:1 (hexanes/ethyl acetate)] to afford 0.518 g (58% yield) of trans-3-(2-acetyl-cyclopropyl)-1-(toluene-4-sulfonyl)-1H-indole-5-carbonitrile as a white solid: LC-MS (column=Phenomenex Luna C18 S10, 3×50 mm, start %B=0, final %B=100, gradient time=2 min, flow rate=5 ml/min) m/e 379 (M+H)+, tR 2.45 min.

Workup

  1. stirringstirred for an additional 3 h at 0° C
  2. customThe cold mixture was quenched with aqueous 1 M hydrochloric acid (200 ml)
  3. extractionextracted with ethyl acetate (3×100 ml)
  4. washThe combined organic extracts were washed with brine (50 ml)
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude reaction mixture
  9. customwas purified by silica gel column chromatography

Sources & evidence

ORD record
ord-8d406143e11845399797386dd7fbd887
Source dataset
uspto-grants-2004_08
Patent number
US06777437B2

Reaction notes

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