1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 4-methyl-N-[2,2,2-trichloro-1-[(Z)-[(cyanoamino)-(pyridin-3-ylamino)methylidene]amino]ethyl]benzamide

HRID 479499Notes

Reaction equation

HRID 479499 reaction equation
[C:1]([NH:3][C:4]([NH:6][C:7]1[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=1)=S)#[N:2].CCN=C=NCCCN(C)C.C(N(C(C)C)CC)(C)C.[NH2:33][CH:34]([NH:39][C:40](=[O:48])[C:41]1[CH:46]=[CH:45][C:44]([CH3:47])=[CH:43][CH:42]=1)[C:35]([Cl:38])([Cl:37])[Cl:36]>CN(C=O)C.C(OCC)(=O)C>[CH3:47][C:44]1[CH:45]=[CH:46][C:41]([C:40]([NH:39][CH:34]([NH:33][C:4](=[N:3][C:1]#[N:2])[NH:6][C:7]2[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=2)[C:35]([Cl:38])([Cl:36])[Cl:37])=[O:48])=[CH:42][CH:43]=1

Participants

7

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531Diisopropylethylamine2×HCID 18770673N-(1-amino-2,2,2-trichloroethyl)-4-methylbenzamideHCID 18770764N-cyano-N'-(3-pyridinyl)thiourea

Product 1

HCID 1784258694-methyl-N-[2,2,2-trichloro-1-[(Z)-[(cyanoamino)-(pyridin-3-ylamino)methylidene]amino]ethyl]benzamideYield 36.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of Example 44A (200 mg, 0.932 mmol) in DMF (7 mL) at 23° C. was treated with EDCI (250 mg, 1.30 mmol) followed by diisopropyethylamine (0.180 mL, 1.03 mmol). The mixture was stirred for 30 minutes, then treated with a solution of Example 38A (262 mg, 0.932 mmol) as a solution in DMF (2 mL) along with additonal diisopropyethylamine (0.360 mL, 2.06 mmol). The solution was stirred for 10 hours, poured into ethyl acetate (25 mL), and washed with water (25 mL). The aqueous layer was extracted with ethyl acetate (20 mL), and the combined organic portions were washed with water (3×20 mL) and brine (20 mL). The organic portion was dried (Na2SO4), filtered, and concentrated. Purification of the residue by flash chromatography (elution with 5% ethanol/hexanes) provided 146 mg of the desired product as an off-white solid.

Workup

  1. stirringThe solution was stirred for 10 hours
  2. washwashed with water (25 mL)
  3. extractionThe aqueous layer was extracted with ethyl acetate (20 mL)
  4. washthe combined organic portions were washed with water (3×20 mL) and brine (20 mL)
  5. dry with materialThe organic portion was dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification of the residue
  9. washby flash chromatography (elution with 5% ethanol/hexanes)

Sources & evidence

ORD record
ord-0db2a288bafc43e3ab55640b0c826992
Source dataset
uspto-grants-2003_11
Patent number
US06645968B2

Reaction notes

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