Sodium Chloride → HCID 13192392, compound

HRID 1761462Notes

Reaction equation

HRID 1761462 reaction equation
CO[C:3]([CH:5]1[CH:19]=[C:18]2[C@@H:8]([CH2:9][C:10]3[C:20]4[C:13](=[CH:14][CH:15]=[CH:16][C:17]2=4)[NH:12][CH:11]=3)[N:7]([C:21]#[N:22])[CH2:6]1)=[O:4].[NH2:23][NH2:24].[Cl-].[Na+].C(Cl)Cl>C(Cl)(Cl)Cl>[C:21]([N:7]1[C@H:8]2[C:18]([C:17]3[CH:16]=[CH:15][CH:14]=[C:13]4[C:20]=3[C:10]([CH2:9]2)=[CH:11][NH:12]4)=[CH:19][CH:5]([C:3]([NH:23][NH2:24])=[O:4])[CH2:6]1)#[N:22]

Participants

6

Reactant 4

HCID 5234Sodium ChlorideHCID 6344DichloromethaneHCID 9321HydrazineHCID 13192390HCID 13192390, compound

Product 1

HCID 13192392HCID 13192392, compound

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

950 mg of 6-cyano-9,10-didehydroergolinecarboxylic acid methyl ester (3.2 mmol) is dissolved in 100 ml of chloroform and 18 ml of anhydrous hydrazine and stirred for one hour in an ice bath and for 3 hours at room temperature. The mixture is distributed between saturated sodium chloride solution and methylene chloride; the organic phase is washed with water, dried with magnesium sulfate, and evaporated (crude product 739 mg). The product is chromatographed on silica gel with methylene chloride, ethyl acetate, and methanol, yielding the pure 6-cyano-9,10-didehydroergolinecarboxylic acid hydrazide. A solution of 950 mg (3.2 mmol) of this hydrazide in 100 ml of tetrahydrofuran is cooled in an ice bath and combined in succession with 11 ml of a saturated solution of hydrogen chloride in toluene (about 0.7N), 3.5 ml of a 1N lithium nitrite solution in tetrahydrofuran, and 22 ml of the above hydrogen chloride solution. Under ice cooling, the mixture is agitated for 20 minutes, then diluted with 140 ml of dioxane, and heated for 30 minutes in an oil bath preheated to 80° C. After cooling in an ice bath, 20 ml of 0.2N hydrochloric acid is added thereto, the mixture is allowed to stand for 20 minutes and evaporated to dryness. The residue is made into a solution with a small amount of methanol, distributed between chloroform and sodium bicarbonate, the aqueous phase is washed with chloroform, the organic phase respectively several times with water, dried with magnesium sulfate, and evaporated. 1.0 g of the crude 8-amino-6-cyano-9,10-didehydroergoline is dissolved in 15 ml of pyridine, combined with 0.6 ml of acetyl chloride, and ice is added after one hour; the mixture is distributed between saturated bicarbonate solution and methylene chloride; the organic phase is dried and evaporated.

Workup

  1. washthe organic phase is washed with water
  2. dry with materialdried with magnesium sulfate
  3. customevaporated (crude product 739 mg)
  4. customThe product is chromatographed on silica gel with methylene chloride, ethyl acetate, and methanol

Sources & evidence

ORD record
ord-7f24e4c995df4a40a89029d744b1029d
Source dataset
uspto-grants-1989_05
Patent number
US04826852

Reaction notes

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