1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → HCID 67960517, compound

HRID 1895791Notes

Reaction equation

HRID 1895791 reaction equation
[CH:1]([C:3]1[CH:8]=[CH:7][N:6]=[C:5]([CH2:9][O:10][C:11]([C@@H:13]2[CH2:18][CH2:17][CH2:16][N:15]([C:19](=[O:46])[C@@H:20]([NH:36][C:37](=[O:45])[C@@H:38]([NH:42][CH:43]=[O:44])[CH:39]([CH3:41])[CH3:40])[CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([O:28][Si:29]([C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:31])[CH3:30])[CH:23]=3)[NH:14]2)=[O:12])[CH:4]=1)=[CH2:2].[CH3:47][O:48][C@H:49]([CH2:55][CH2:56][CH:57]=[CH2:58])[C@@H:50](C)[C:51](O)=O.Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1>C(#N)C>[CH:1]([C:3]1[CH:8]=[CH:7][N:6]=[C:5]([CH2:9][O:10][C:11]([C@@H:13]2[CH2:18][CH2:17][CH2:16][N:15]([C:19](=[O:46])[C@@H:20]([NH:36][C:37](=[O:45])[C@@H:38]([NH:42][C:43](=[O:44])[C@H:50]([CH3:51])[C@H:49]([O:48][CH3:47])[CH2:55][CH2:56][CH:57]=[CH2:58])[CH:39]([CH3:41])[CH3:40])[CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([O:28][Si:29]([C:32]([CH3:33])([CH3:34])[CH3:35])([CH3:31])[CH3:30])[CH:23]=3)[NH:14]2)=[O:12])[CH:4]=1)=[CH2:2]

Participants

6

Reactant 4

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 86675865HCID 86675865, compoundHCID 86675866HCID 86675866, compound

Product 1

HCID 67960517HCID 67960517, compoundYield 67%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of crude (S)-1-[(S)-3-[3-(tert-butyl-dimethyl-silanyloxy)-phenyl]-2-((S)-2-formylamino-3-methyl-butyrylamino)-propionyl]-hexahydro-pyridazine-3-carboxylic acid 4-vinyl-pyridin-2-ylmethyl ester (0.52 mmol) and (2R,3R)-3-methoxy-2-methylhept-6-enoic acid 10d (90 mg, 0.52 mmol) in acetonitrile (10 mL) was stirred at room temperature. N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (140 mg, 0.73 mmol) and 1-hydroxybenzotriazole hydrate (containing 20% water, 85 mg, 0.52 mmol) was added and the reaction mixture was stirred at room temperature for 4 hours. The solvent was evaporated and the residue was partitioned between ethyl acetate and water. The organic extract was separated, washed with brine, dried over anhydrous sodium sulfate and evaporated. The residue was purified by silica gel chromatography using a gradient of iso-hexanes/ethyl acetate 1:3 to neat ethyl acetate to afford the title compound (271 mg, 67%) as a gum. 1H NMR (300 MHz, CDCl3) δ 0.17 (s, 6H), 0.86-0.98 (m, 15H), 1.17 (d, J=7.1 Hz, 3H), 1.5-2.2 (m, 11H), 2.45-3.00 (m, 5H), 3.33-3.44 (m, 1H), 3.40 (s, 3H), 3.60 (d, J=10.9 Hz, 1H), 4.27-4.33 (m, 2H), 4.97 (dd, J=10.2, 1.7 Hz, 1H), 5.05 (dd, J=17.2, 1.7 Hz, 1H), 5.28 (d, J=7.3 Hz, 1H), 5.56 (d, J=10.7 Hz, 1H), 5.73-5.87 (m, 2H), 6.03 (d, J=17.6 Hz, 1H), 6.50 (d, J=8.2 Hz, 2H), 6.66-6.82 (m, 4H), 7.04-7.10 (m, 1H), 7.31 (s, 1H), 8.56 (d, J=5.1 Hz, 1H). LCMS (m/z) 778 [M+H], Tr=5.78 min.

Workup

  1. stirringthe reaction mixture was stirred at room temperature for 4 hours
  2. customThe solvent was evaporated
  3. customthe residue was partitioned between ethyl acetate and water
  4. extractionThe organic extract
  5. customwas separated
  6. washwashed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. customevaporated
  9. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-bbb3e6e812a4432fa1da6dd4b8060001
Source dataset
uspto-grants-2013_08
Patent number
US08513184B2

Reaction notes

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