L-Glutamic acid, N-((phenylmethoxy)carbonyl)- → HCID 118060472, compound

HRID 627585Notes

Reaction equation

HRID 627585 reaction equation
[C:1]([NH:11][C@H:12]([C:18]([OH:20])=O)[CH2:13][CH2:14][C:15]([OH:17])=O)([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].CN(C(ON1N=N[C:31]2[CH:32]=[CH:33][CH:34]=[N:35][C:30]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)[CH:48]([CH3:50])[CH3:49]>CN(C=O)C.CN(C1C=CN=CC=1)C>[CH2:4]([O:3][C:1]([NH:11][CH:12]1[CH2:13][CH2:14][C:15](=[O:17])[N:35]([CH:34]([CH2:33][CH:32]2[CH2:31][CH2:30][CH2:50][CH2:48][CH2:49]2)[C:1]([O:3][CH3:4])=[O:2])[C:18]1=[O:20])=[O:2])[C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1

Participants

6

Reactant 3

HCID 70866L-Glutamic acid, N-((phenylmethoxy)carbonyl)-2×HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 118060472HCID 118060472, compoundYield 49.9%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent2×

Procedure

To a solution of (L) N-Cbz-glutamic acid (5.62 g; 20 mmol) in dry DMF (100 mL) was added HATU (8.36 g; 22 mmol) and DMAP (0.56 g) followed by the dropwise addition of TEA (6 mL; 44 mmol). The reaction mixture was stirred at room temperature for 1 h (solution A). In the meantime, to a solution of (L) cyclohexylalanine-OMe(HCl) (5.32 g; 24 mmol) in dry DMF (30 mL) was added DIEA (9.28 g; 72 mmol) and the reaction mixture was stirred for 15 min (solution B). Solution B was mixed with solution A and stirred overnight at room temperature. The solvent was removed on the rotary evaporator and the residue was taken up in ethyl acetate (300 mL). The organic layer was washed sequentially with saturated sodium bicarbonate (2×100 mL), 5% HCl (2×100 mL) and brine (100 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated, yielding a crude product which was purified by flash chromatography (silica gel; hexane/ethyl acetate 75:25) to give 1 as a white solid (2.15 g; 32% yield). 1H NMR (CDCl3): δ 8.0 (s, 1H), 7.32 (m, 5H), 5.04 (m, 2H), 4.62 (m, 1H), 4.0 (m 1H), 3.73 (s, 3H), 2.3 (m, 2H), 2.0 (m, 2H), 1.65 (m, 6H), 1.46 (m, 1H), 1.18 (m, 4H), 0.89 (m, 2H).

Workup

  1. customThe solvent was removed on the rotary evaporator
  2. washThe organic layer was washed sequentially with saturated sodium bicarbonate (2×100 mL), 5% HCl (2×100 mL) and brine (100 mL)
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customyielding a crude product which
  7. customwas purified by flash chromatography (silica gel; hexane/ethyl acetate 75:25)

Sources & evidence

ORD record
ord-2004c6ba3f5f49678595db085d036150
Source dataset
uspto-grants-2016_04
Patent number
US09309284B2

Reaction notes

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