Hydrochloric Acid → 2-(5-[(1S)-1-benzyloxycarbonylamino-ethyl]-3-benzyl-2-oxo-cyclohept-4-en-1-yl)-1-oxo-ethyl-valinyl-valine methyl ester

HRID 1755818Notes

Reaction equation

HRID 1755818 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:14]1[CH2:20][CH2:19][CH:18]([CH2:21][C:22](O)=[O:23])[C:17](=[O:25])[CH:16]([CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:15]=1)[CH3:13])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.OC1C2N=NNC=2C=CC=1.Cl.[NH2:44][C@H:45]([C:49]([NH:51][C@H:52]([C:56]([O:58][CH3:59])=[O:57])[CH:53]([CH3:55])[CH3:54])=[O:50])[CH:46]([CH3:48])[CH3:47].CN([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F>CN(C)C=O.C(N(CC)CC)C>[CH3:59][O:58][C:56](=[O:57])[C@H:52]([CH:53]([CH3:54])[CH3:55])[NH:51][C:49](=[O:50])[C@H:45]([CH:46]([CH3:48])[CH3:47])[NH:44][C:22](=[O:23])[CH2:21][CH:18]1[CH2:19][CH2:20][C:14]([C@@H:12]([NH:11][C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[O:10])[CH3:13])=[CH:15][CH:16]([CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:17]1=[O:25]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 12944632L-valyl L-valine methyl esterHCID 54027587(5-[(1S)-1-benzyloxycarbonylamino-ethyl]-3-benzyl-2-oxo-cyclohept-4-en-1-yl)-ethanoic acidHCID 178418300HCID 178418300, compound

Product 1

HCID 677819852-(5-[(1S)-1-benzyloxycarbonylamino-ethyl]-3-benzyl-2-oxo-cyclohept-4-en-1-yl)-1-oxo-ethyl-valinyl-valine methyl esterYield 63.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

To a stirred solution of the above acid (37) (1.0 g) in dimethylformamide (20 mL) was added hydroxybenzotriazole (0.62 g), HCl.Val-Val-OMe (0.67 g), triethylamine (1.93 mL) followed by Bop reagent (1.93 g). After stirring at room temperature for 16 h the reaction was evaporated to dryness and flash chromatographed on silica gel eluted with 60% ethyl acetate in n-hexane to give the titled product (38) (0.95 g, 57%). TLC Rf 0.48, 0.41 (60% ethyl acetate, n-hexane) Rf 0.40, 0.37 (97:3 CHCl3 :MeOH); MS DCI/NH3 (M+H)+ =648.5; 1H NMR (CDCl3) δ0.8-1.0(12H, m) Val γ(CH3)2 's, 1.12(3H, d, J=7 Hz) Ala CH3, 3.7(3H, s) CO2CH3, 5.1(2H, s) Cbz CH2, 5.4(1H, d) vinyl CH, 7.22(5H, s) phenyl, 7.46(5H, s) Cbz phenyl.

Workup

  1. customwas evaporated to dryness and flash
  2. customchromatographed on silica gel
  3. washeluted with 60% ethyl acetate in n-hexane

Sources & evidence

ORD record
ord-d5ebbab86fca4bbcbf8462e531c85091
Source dataset
uspto-grants-1995_08
Patent number
US05438118

Reaction notes

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