Diisopropylethylamine → HCID 118175673, compound

HRID 2176210Notes

Reaction equation

HRID 2176210 reaction equation
[C:1]([N:9]([CH3:30])[C@@H:10]([CH:27]([CH3:29])[CH3:28])[C:11]([NH:13][C@@H:14]([CH3:26])[C:15]([N:17]1[CH2:22][CH2:21][CH2:20][C@@H:19]([C:23](O)=[O:24])[NH:18]1)=[O:16])=[O:12])(=[O:8])[CH2:2][CH2:3][CH2:4][CH2:5][CH:6]=[CH2:7].C([N:34](CC)[CH:35]([CH3:37])[CH3:36])(C)C.C[NH3+].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)[C:53]2N=[CH:55][CH:56]=[CH:57][C:52]=2N=N1.F[P-](F)(F)(F)(F)F>C(#N)C>[CH:27]([C@@H:10]1[N:9]([CH3:30])[C:1](=[O:8])[CH2:2][CH2:3][CH2:4][CH2:5][CH:6]=[CH:7][C:52]2[CH:53]=[C:37]([CH:55]=[CH:56][CH:57]=2)[C@@H:35]([CH3:36])[NH:34][C:23](=[O:24])[C@H:19]2[NH:18][N:17]([CH2:22][CH2:21][CH2:20]2)[C:15](=[O:16])[C@H:14]([CH3:26])[NH:13][C:11]1=[O:12])([CH3:28])[CH3:29]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 866211442-(1H-7-Azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate MethanaminiumHCID 131732991HCID 131732991, compound

Product 1

HCID 118175673HCID 118175673, compoundYield 51.9%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 17b (710 mg, 1.3 mmol) in tetrahydrofuran (30 mL) was stirred at room temperature under nitrogen. Zinc dust (1.86 g, 28.6 mmol) was added followed by a solution of ammonium acetate (1.50 g, 19.5 mmol) in water (20 mL) and the reaction mixture was stirred at room temperature for 24 hours. The reaction mixture was filtered through Celite and the filter pad was washed with ethyl acetate and potassium hydrogen sulfate solution (pH ˜2). The filtrate was acidified to pH 2 with 2 M hydrochloric acid and the mixture was extracted with ethyl acetate. The organic extracts were combined, washed with water and brine, dried over anhydrous sodium sulfate, filtered and evaporated. The residue was co-evaporated with toluene and dried to afford (S)-1-{(S)-2-[(S)-2-(hept-6-enoyl-methyl-amino)-3-methyl-butyrylamino]-propionyl}-hexahydro-pyridazine-3-carboxylic acid (468 mg, 85%) as a gum. A solution of (S)-1-{(S)-2-[(S)-2-(hept-6-enoyl-methyl-amino)-3-methyl-butyrylamino]propionyl}-hexahydropyridazine-3-carboxylic acid (468 mg, 1.1 mmol) in acetonitrile (25 mL) was stirred at room temperature under nitrogen. 1j (200 mg, 1.1 mmol) and N,N-diisopropylethylamine (710 mg, 1.0 mL, 5.5 mmol) was added followed by 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate methanaminium (585 mg, 1.54 mmol) and the reaction mixture was stirred at room temperature for 72 hours. The solvent was evaporated and the residue was dissolved in ethyl acetate. The solution was washed with 2 M hydrochloric acid, water, saturated sodium hydrogen carbonate solution, water and brine, dried over anhydrous sodium sulfate, filtered and evaporated. The residue was purified by silica gel chromatography using a gradient of iso-hexanelethyl acetate 1:1 to ethyl acetate to afford the title compound as a white solid (300 mg, 49%).

Workup

  1. customThe solvent was evaporated
  2. dissolutionthe residue was dissolved in ethyl acetate
  3. washThe solution was washed with 2 M hydrochloric acid, water, saturated sodium hydrogen carbonate solution, water and brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-845aa3bdb03d44c78199dc947d94584f
Source dataset
uspto-grants-2015_06
Patent number
US09062092B2

Reaction notes

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