6-Heptenoic acid → HCID 118175673, compound

HRID 2176209Notes

Reaction equation

HRID 2176209 reaction equation
ClC(Cl)(Cl)CO[C:5]([C@@H:7]1[CH2:12][CH2:11][CH2:10][N:9]([C:13](=[O:25])[C@@H:14]([NH:16][C:17](=[O:24])[C@@H:18]([NH:22][CH3:23])[CH:19]([CH3:21])[CH3:20])[CH3:15])[NH:8]1)=[O:6].[C:28]([OH:36])(=O)[CH2:29][CH2:30][CH2:31][CH2:32][CH:33]=[CH2:34].C([N:40](CC)[CH:41]([CH3:43])[CH3:42])(C)C.C[NH3+].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)[C:59]2N=[CH:61][CH:62]=[CH:63][C:58]=2N=N1.F[P-](F)(F)(F)(F)F>C(#N)C>[CH:19]([C@@H:18]1[N:22]([CH3:23])[C:28](=[O:36])[CH2:29][CH2:30][CH2:31][CH2:32][CH:33]=[CH:34][C:58]2[CH:59]=[C:43]([CH:61]=[CH:62][CH:63]=2)[C@@H:41]([CH3:42])[NH:40][C:5](=[O:6])[C@H:7]2[NH:8][N:9]([CH2:10][CH2:11][CH2:12]2)[C:13](=[O:25])[C@H:14]([CH3:15])[NH:16][C:17]1=[O:24])([CH3:20])[CH3:21]

Participants

6

Reactant 4

HCID 707056-Heptenoic acidHCID 81531DiisopropylethylamineHCID 866211442-(1H-7-Azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate MethanaminiumHCID 126629590HCID 126629590, compound

Product 1

HCID 118175673HCID 118175673, compoundYield 77.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 17a (950 mg, 1.74 mmol) in dichloromethane (25 mL) was stirred at 0° C. under nitrogen. Trimethylsilyl trifluoromethanesulfonate (577 mg, 0.47 mL, 2.6 mmol) was added and the reaction mixture was stirred at 0° C. for 1 h. Additional trimethylsilyl trifluoromethanesulfonate (0.2 mL, 1.1 mmol) was added and the reaction mixture was stirred at 0° C. for 2 h. N,N-diisopropylethylamine (903 mg, 1.2 mL, 7 mmol) was added and the solvent was evaporated and the residue was dried to afford crude (S)-1-[(S)-2-((S)-3-methyl-2-methylamino-butyrylamino)-propionyl]-hexahydro-pyridazine-3-carboxylic acid 2,2,2-trichloro-ethyl ester (1.74 mmol), which was used in the next step. A solution of crude (S)-1-[(S)-2-((S)-3-methyl-2-methylamino-butyrylamino)-propionyl]-hexahydro-pyridazine-3-carboxylic acid 2,2,2-trichloro-ethyl ester (1.74 mmol) in acetonitrile (20 mL) was stirred at 0° C. under nitrogen. Hept-6-enoic acid (268 mg, 0.3 mL, 2.1 mmol) and N,N-diisopropylethylamine (903 mg, 1.2 mL, 7 mmol) were added. 2-(1H-7-Azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate methanaminium (912 mg, 2.4 mmol) was added and the reaction mixture was stirred at room temperature for 18 h. The solvent was evaporated and the residue was diluted with ethyl acetate. The solution was washed with saturated sodium hydrogen carbonate solution, water, 2 M hydrochloric acid, 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 3:1 to 1:1 to afford the title compound (710 mg, 74%) as a white solid.

Workup

  1. customThe solvent was evaporated
  2. additionthe residue was diluted with ethyl acetate
  3. washThe solution was washed with saturated sodium hydrogen carbonate solution, water, 2 M hydrochloric acid, 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-d563429c34db48169181a3e14e2fd067
Source dataset
uspto-grants-2015_06
Patent number
US09062092B2

Reaction notes

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