1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → Methyl 11-(3((3-azidopropyl)amino)-3-oxopropyl)-8-isobutyl-3,6,9-trioxo-1-phenyl-5-(prop-2-yn-1-yl)-2-oxa-4,7,10-triazadodecan-12-oate

HRID 627583Notes

Reaction equation

HRID 627583 reaction equation
[CH2:1]([O:8][C:9]([NH:11][CH:12]([CH2:24][C:25]#[CH:26])[C:13]([NH:15][CH:16]([CH2:20][CH:21]([CH3:23])[CH3:22])[C:17]([OH:19])=O)=[O:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[Cl-].[N:49]([CH2:52][CH2:53][CH2:54][NH:55][C:56](=[O:65])[CH2:57][CH2:58][CH:59]([NH3+:64])[C:60]([O:62][CH3:63])=[O:61])=[N+:50]=[N-:51].CCN(C(C)C)C(C)C>CN(C=O)C>[N:49]([CH2:52][CH2:53][CH2:54][NH:55][C:56](=[O:65])[CH2:57][CH2:58][CH:59]([C:60]([O:62][CH3:63])=[O:61])[NH:64][C:17](=[O:19])[CH:16]([CH2:20][CH:21]([CH3:23])[CH3:22])[NH:15][C:13](=[O:14])[CH:12]([CH2:24][C:25]#[CH:26])[NH:11][C:9](=[O:10])[O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[N+:50]=[N-:51]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 781061162-(2-(((Benzyloxy)carbonyl)amino)pent-4-ynamido)-4-methylpentanoic acidHCID 900104115-((3-Azidopropyl)amino)-1-methoxy-1,5-dioxopentan-2-aminium chloride

Product 1

HCID 78148732Methyl 11-(3((3-azidopropyl)amino)-3-oxopropyl)-8-isobutyl-3,6,9-trioxo-1-phenyl-5-(prop-2-yn-1-yl)-2-oxa-4,7,10-triazadodecan-12-oateYield 46%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of compound 4 (11.7 g; 31 mmol) in dry DMF (100 mL) was added EDCI (7.25 g; 37.82 mmol), HOBt (5.79 g; 37.82 mmol), and the reaction mixture was stirred at room temperature for 30 min (solution A). In the meantime, to a solution of compound 9 (8.67 g: 31 mmol) in dry DMF (100 mL) kept at 0° C. was added DIEA (10.01 g; 77.7 mmol) and stirred for 30 min (solution B). Solution B was mixed with solution A and the reaction mixture was stirred overnight at room temperature. The solvent was removed on the rotary evaporator and the residue was taken up in ethyl acetate (300 mL) and washed sequentially with saturated sodium bicarbonate (2×75 mL), 5% HCl (2×75 mL) and brine (75 mL). The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated, yielding a crude product which was purified using recrystallization to yield 9 as an off white solid (8.3 g; 46% yield). NMR (CDCl3) δ 8.1 (s, 1H), 7.9 (s, 1H), 7.8 (s, 1H), 7.5 (s, 1H) 7.3 (m, 5H), 5.0 (s, 2H), 4.3 (m, 1H), 4.1 (m, 1H), 3.3 (t, 1H), 2.8 (s, 1H), 2.4 (d, 2H), 2.2 (d, 2H), 2.1 (m, 2H), 1.9 (m, 2H), 1.8 (m, 2H), 1.6 (m, 2H), 1.4 (m, 1H), 0.8 (d, 6H)

Workup

  1. customkept at 0° C.
  2. customThe solvent was removed on the rotary evaporator
  3. washwashed sequentially with saturated sodium bicarbonate (2×75 mL), 5% HCl (2×75 mL) and brine (75 mL)
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-c146d1af1d7a4dcaa04f0e93abce70c4
Source dataset
uspto-grants-2016_04
Patent number
US09309284B2

Reaction notes

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