1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 86675871, compound

HRID 1895800Notes

Reaction equation

HRID 1895800 reaction equation
[CH:1]([C:3]1[CH:4]=[C:5]([C@H:9]([O:11][C:12]([C@@H:14]2[CH2:19][CH2:18][CH2:17][N:16]([C:20](=[O:52])[C@@H:21]([NH:37][C:38](=[O:51])[C@@H:39]([NH:43][C:44](OC(C)(C)C)=[O:45])[CH:40]([CH3:42])[CH3:41])[CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([O:29][Si:30]([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31])[CH:24]=3)[NH:15]2)=[O:13])[CH3:10])[CH:6]=[CH:7][CH:8]=1)=[CH2:2].[CH:53](N(CC)C(C)C)(C)C.C(N=C=NCCCN(C)C)C.[OH:73][C:74]1[C:82]2N=NN[C:78]=2[CH:77]=[CH:76][CH:75]=1>ClCCl>[CH:8]([C:3]1[CH:4]=[C:5]([C@H:9]([O:11][C:12]([C@@H:14]2[CH2:19][CH2:18][CH2:17][N:16]([C:20](=[O:52])[C@@H:21]([NH:37][C:38](=[O:51])[C@@H:39]([NH:43][C:44](=[O:45])[CH2:75][C@H:74]([O:73][CH3:53])[CH2:82][CH2:78][CH:77]=[CH2:76])[CH:40]([CH3:42])[CH3:41])[CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([O:29][Si:30]([C:33]([CH3:34])([CH3:35])[CH3:36])([CH3:31])[CH3:32])[CH:24]=3)[NH:15]2)=[O:13])[CH3:10])[CH:6]=[CH:2][CH:1]=1)=[CH2:7]

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 86675872HCID 86675872, compoundHCID 178418300HCID 178418300, compound

Product 1

HCID 86675871HCID 86675871, compoundYield 32%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A stirred solution of (S)-1-{(S)-2-((S)-2-tert-butoxycarbonylamino-3-methyl-butyrylamino)-3-[3-(tert-butyl-dimethyl-silanyloxy)-phenyl]-propionyl}-hexahydro-pyridazine-3-carboxylic acid (R)-1-(3-vinyl-phenyl)-ethyl ester (367 mg, 0.50 mmol) in anhydrous dichloromethane (10 mL) was cooled to 0° C. then treated with trimethylsilyl trimethanesulfonate (135 μL, 2.0 mmol). The reaction mixture was stirred at 0° C. for 1.5 hours, then N,N-diisopropylethylamine (350 μL, 2.0 mmol) was added and the mixture was evaporated. The residue was dissolved in acetonitrile (5 mL) and (R)-3-methoxy-hept-6-enoic acid was added followed by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (134 mg, 0.70 mmol) and hydroxybenzotriazole (81 mg, 0.50 mmol). The reaction was stirred at room temperature under a nitrogen atmosphere for 16 hours. It was then evaporated to dryness before partitioning between ethyl acetate (20 mL) and water (20 mL). The aqueous was extracted with further ethyl acetate (20 mL), the organic layers were combined, dried over anhydrous sodium sulfate, filtered and evaporated. The residue was purified by silica gel chromatography using ethyl acetate/iso-hexanes 13:7 to give the title compound (123 mg, 32%) as a colourless solid. 1H NMR (300 MHz, CDCl3) δ 0.16 (s, 6H), 0.80-1.00 (m, 17H), 1.34-1.94 (m, 12H), 2.00-2.20 (m, 5H), 2.34-2.53 (m, 3H), 2.63-3.03 (m, 3H), 3.38 (s, 3H), 3.52-3.70 (m, 2H), 4.27-4.38 (m, 2H), 4.92-5.10 (m, 2H), 5.29 (d, J=10.9 Hz, 1H), 5.64-5.98 (m, 2H), 6.52-6.99 (m, 4H), 7.22-7.42 (m, 2H). LCMS (m/z) 777.0 [M+H] Tr=5.96 min.

Workup

  1. customthe mixture was evaporated
  2. dissolutionThe residue was dissolved in acetonitrile (5 mL)
  3. addition(R)-3-methoxy-hept-6-enoic acid was added
  4. stirringThe reaction was stirred at room temperature under a nitrogen atmosphere for 16 hours
  5. customIt was then evaporated to dryness
  6. custombefore partitioning between ethyl acetate (20 mL) and water (20 mL)
  7. extractionThe aqueous was extracted with further ethyl acetate (20 mL)
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. customevaporated
  11. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-d53148315ca64e13aaf2198717ed1fb1
Source dataset
uspto-grants-2013_08
Patent number
US08513184B2

Reaction notes

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