Dimethylformamide → Methyl 2-(2-((tert-butoxycarbonyl)amino)pent-4-ynamido)-4-methylpentanoate

HRID 627582Notes

Reaction equation

HRID 627582 reaction equation
[C:1]([NH:8][C@H:9]([C:15]([O:17]C)=O)[CH2:10][CH2:11][C:12](=O)O)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CCN=C=N[CH2:24][CH2:25][CH2:26]N(C)C.C1C=CC2N([OH:39])N=NC=2C=1.[Cl-].N(CCC[NH3+])=[N+]=[N-].CC[N:50]([CH:54]([CH3:56])[CH3:55])C(C)C.CN([CH:60]=[O:61])C>>[C:4]([O:3][C:1]([NH:8][CH:9]([CH2:10][C:11]#[CH:12])[C:15]([NH:50][CH:54]([CH2:55][CH:25]([CH3:26])[CH3:24])[C:56]([O:61][CH3:60])=[O:39])=[O:17])=[O:2])([CH3:5])([CH3:6])[CH3:7]

Participants

7

Reactant 6

HCID 6228Dimethylformamide2×HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 7018754(4S)-4-(((tert-butoxy)carbonyl)amino)-5-methoxy-5-oxopentanoic acidHCID 1317353223-Azidopropan-1-aminium chloride

Product 1

HCID 90010236Methyl 2-(2-((tert-butoxycarbonyl)amino)pent-4-ynamido)-4-methylpentanoateYield 67%

Procedure

To a solution of (L) BocNH-Glu-OMe (9.67 g; 37 mmol) in dry DMF (100 mL) was added EDCI (8.65 g; 41.1 mmol), HOBt (6.91 g; 45.14 mmol), and the reaction mixture was stirred at room temperature for 1 h (solution A). In the meantime, to a solution of compound 7 (5.05 g: 37 mmol) in dry DMF (50 mL) kept at 0° C. was added DIEA (23.9 g; 185 mmol) and stirred for 30 min (solution B). Solution B was added to 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 DCM (400 mL) and washed sequentially with 10% citric acid (100 mL) and brine (100 mL). The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated, yielding a crude product was purified by flash chromatography (silica gel; hexane/ethyl acetate 70:30) to give 1 as a white solid (8.6 g; 67% yield). 1H NMR (CDCl3) δ 7.8 (s, 1H), 7.4 (s, 1H), 4.6 (m, 1H), 3.7 (s, 3H), 3.3 (t, 1H), 2.2 (m, 2H), 2.1 (m, 2H), 1.9 (m, 2H), 1.7 (m, 2H), 1.4 (s, 9H).

Workup

  1. customkept at 0° C.
  2. customThe solvent was removed on the rotary evaporator
  3. washwashed sequentially with 10% citric acid (100 mL) and brine (100 mL)
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customyielding a crude product
  8. customwas purified by flash chromatography (silica gel; hexane/ethyl acetate 70:30)

Sources & evidence

ORD record
ord-1fc88c2878b54db1b3d202225eea19d9
Source dataset
uspto-grants-2016_04
Patent number
US09309284B2

Reaction notes

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