Diisopropylethylamine → HCID 178422295, compound

HRID 2182371Notes

Reaction equation

HRID 2182371 reaction equation
Cl.CN(C)CCCN=C=NCC.C(N(C(C)C)CC)(C)C.[CH3:22][C:23]1[C:37]([CH3:38])=[CH:36][C:26]2[NH:27][C:28]([C:30]3[C:34]([NH2:35])=[CH:33][NH:32][N:31]=3)=[N:29][C:25]=2[CH:24]=1.[N:39]1([CH2:44][C:45](O)=[O:46])[CH:43]=[N:42][N:41]=[N:40]1>CN(C)C=O>[CH3:38][C:37]1[C:23]([CH3:22])=[CH:24][C:25]2[NH:29][C:28]([C:30]3[C:34]([NH:35][C:45](=[O:46])[CH2:44][N:39]4[CH:43]=[N:42][N:41]=[N:40]4)=[CH:33][NH:32][N:31]=3)=[N:27][C:26]=2[CH:36]=1

Participants

6

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 5432071-Tetrazolylacetic acid2×HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride2×HCID 178422296HCID 178422296, compound

Product 1

HCID 178422295HCID 178422295, compoundYield 9.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A stirred solution of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (295.7 mg) and diisopropylethylamine (269 μl) in dimethylformamide (10 ml) were treated with 3-(5,6-dimethyl-1H-benzoimidazol-2-yl)-1H-pyrazol-4-ylamine [100 mg, Example 233(c)] and 2-(1H-1,2,3,4-tetraazol-1-yl) acetic acid (197.8 mg). The reaction mixture was stirred for 72 hours then treated further with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (295.7 mg), diisopropylethylamine (269 μl) and 2-(1H-1,2,3,4-tetraazol-1-yl) acetic acid (197.8 mg). Stirring was continued for a further 48 hours then the reaction mixture was partitioned between ethyl acetate and water. The organic phase was evaporated and the residue was treated with 1N potassium hydroxide in a mixture of methanol and tetrahydrofuran (1:4, 8 ml). After 1 hour this mixture was extracted with ethyl acetate. The extract was washed with brine, then dried over magnesium sulfate and then evaporated to dryness. The residue was subjected to preparative HPLC to give N-[3-(5,6-dimethyl-1H-benzoimidazol-2-yl)-1H-pyrazol-4-yl]-2-(1H-1,2,3,4-tetraazol-1-yl)-acetamide (13.7 mg) as an off-white solid. MS: 338.14 (M+H)+. HPLC (METHOD B1): RT=7.26 minutes. (b) N-[3-(5,6-Dimethyl-1H-benzoimidazol-2-yl)-1H-pyrazol-4-yl]-isonicotinamide

Workup

  1. stirringStirring
  2. waitwas continued for a further 48 hours
  3. customthe reaction mixture was partitioned between ethyl acetate and water
  4. customThe organic phase was evaporated
  5. additionthe residue was treated with 1N potassium hydroxide in a mixture of methanol and tetrahydrofuran (1:4, 8 ml)
  6. extractionAfter 1 hour this mixture was extracted with ethyl acetate
  7. washThe extract was washed with brine
  8. dry with materialdried over magnesium sulfate
  9. customevaporated to dryness

Sources & evidence

ORD record
ord-4c207d13dc534109bbc8dd7f8454d985
Source dataset
uspto-grants-2005_05
Patent number
US06897208B2

Reaction notes

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