Ammonia → 3-(13-Nitro-6-methyl-8alpha-ergolinyl)-1,1-diethylurea

HRID 1073300Notes

Reaction equation

HRID 1073300 reaction equation
[CH3:1][N:2]1[C@H:16]2[C@@H:6]([C:7]3[CH:8]=[C:9]([N+:18]([O-:20])=[O:19])[CH:10]=[C:11]4[C:17]=3[C@H:14]([CH2:15]2)[CH2:13][NH:12]4)[CH2:5][C@H:4]([NH:21][C:22](=[O:28])[N:23]([CH2:26][CH3:27])[CH2:24][CH3:25])[CH2:3]1.ClOC(C)(C)C.N>O1CCCC1.C(N(CC)CC)C>[CH3:1][N:2]1[C@H:16]2[C@@H:6]([C:7]3[CH:8]=[C:9]([N+:18]([O-:20])=[O:19])[CH:10]=[C:11]4[C:17]=3[C:14]([CH2:15]2)=[CH:13][NH:12]4)[CH2:5][C@H:4]([NH:21][C:22](=[O:28])[N:23]([CH2:26][CH3:27])[CH2:24][CH3:25])[CH2:3]1

Participants

6

Reactant 3

HCID 222AmmoniaHCID 521297Tert-Butyl hypochloriteHCID 13374954HCID 13374954, compound

Product 1

HCID 133749573-(13-Nitro-6-methyl-8alpha-ergolinyl)-1,1-diethylureaYield 71.7%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8471TriethylamineSolvent

Conditions

Temperature
-40 °C

Procedure

Under argon, 382 mg (1 mmol) of 3-(2,3β-dihydro-6-methyl-13-nitro-8α-ergolinyl)-1,1-diethylurea is dissolved in 30 ml of absolute, freshly distilled tetrahydrofuran in the presence of 0.5 ml of triethylamine and cooled to -40° C. At this temperature, 0.16 ml (1.34 mmol) of tert-butyl hypochlorite, dissolved in 10 ml of absolute, freshly distilled tetrahydrofuran, is added dropwise thereto. After 30 minutes of agitation at -40° C., the batch is stirred into 50 ml of ice and adjusted to be alkaline with 25% strength ammonia solution. Extraction is performed with methylene chloride. The combined organic phases are dried over magnesium sulfate and concentrated. The crude product is chromatographed under pressure on silica gel, with methylene chloride/methanol/diisopropyl ether in a ratio of 80:5:15 (yield 351 mg) and subsequently crystallized from ethyl acetate/diisopropyl ether, thus obtaining 272 mg of 3-(6-methyl-13-nitro-8α-ergolinyl)-1,1-diethylurea (71.7% yield).

Workup

  1. additionis added dropwise
  2. extractionExtraction
  3. dry with materialThe combined organic phases are dried over magnesium sulfate
  4. concentrationconcentrated
  5. customThe crude product is chromatographed under pressure on silica gel, with methylene chloride/methanol/diisopropyl ether in a ratio of 80:5:15 (yield 351 mg)
  6. customsubsequently crystallized from ethyl acetate/diisopropyl ether

Sources & evidence

ORD record
ord-90e302fc501443948865d1a1676df1ce
Source dataset
uspto-grants-1990_11
Patent number
US04968801

Reaction notes

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