L-Pyroglutamic Acid → N-[1-(L-Pyroglutamyl)pyrrolidin-2(S)-ylmethyl]-N-(1-naphthylmethyl)glycyl-methionine methyl ester

HRID 2258597Notes

Reaction equation

HRID 2258597 reaction equation
Cl.[CH3:2][O:3][C:4](=[O:32])[C@H:5]([CH2:28][CH2:29][S:30][CH3:31])[NH:6][C:7](=[O:27])[CH2:8][N:9]([CH2:21][C@@H:22]1[CH2:26][CH2:25][CH2:24][NH:23]1)[CH2:10][C:11]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:14]=[CH:13][CH:12]=1.[NH:33]1[C:37](=[O:38])[CH2:36][CH2:35][C@H:34]1[C:39](O)=[O:40].C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[Cl-]>CN(C=O)C>[CH3:2][O:3][C:4](=[O:32])[C@H:5]([CH2:28][CH2:29][S:30][CH3:31])[NH:6][C:7](=[O:27])[CH2:8][N:9]([CH2:21][C@@H:22]1[CH2:26][CH2:25][CH2:24][N:23]1[C:39](=[O:40])[C@@H:34]1[CH2:35][CH2:36][C:37](=[O:38])[NH:33]1)[CH2:10][C:11]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:14]=[CH:13][CH:12]=1

Participants

6

Reactant 4

HCID 7405L-Pyroglutamic AcidHCID 81531DiisopropylethylamineHCID 67585810N-(pyrrolidin-2(S)-ylmethyl)-N-(1-naphthylmethyl)-glycyl-methionine methyl ester hydrochlorideHCID 131720136BOP chloride

Product 1

HCID 22876019N-[1-(L-Pyroglutamyl)pyrrolidin-2(S)-ylmethyl]-N-(1-naphthylmethyl)glycyl-methionine methyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N-(Pyrrolidin-2(S)-ylmethyl)-N-(1-naphthylmethyl)-glycyl-methionine methyl ester hydrochloride(0.200 g, 0.387 mmol), L-pyroglutamic acid (0.060 g, 0.465 mmol) and diisopropylethylamine (0.300 mL, 2.32 mmol) were dissolved in dry DMF (2 mL). BOP-chloride (0.355 mg, 1.39 mmol) was added and the mixture stirred under Ar for 18 h. The solvent was removed in vacuo and the residue partitioned between saturated NaHCO3 soln and EtOAc. The layers were separated and the organics were washed with H2O, brine, dried over MgSO4, filtered and the solvent removed in vacuo to give an oil which was chromatographed on silica gel (3:97 MeOH:CH2Cl2) to give the title compound. 1H NMR (CD3OD) δ 8.33 (d, 1H, J=8 Hz), 7.91 (d, 1H, J=7 Hz), 7.85 (d, 1H, J=8 Hz), 7.43-7.64 (m, 4H), 4.36-4.54 (m, 3H), 3.98 (d, 1H, J=13 Hz), 3.69 (s, 3H), 3.49-3.58 (m, 1H), 3.21-3.49 (m, 5H), 2.92 (dd, 1H, J=4, 12 Hz), 2.50-2.59 (m, 1H), 2.25-2.50 (m, 3H), 2.08-2.25 (m, 1H), 1.79-2.08 (m, 5H), 1.95 (s, 3H), 1.70-1.79 (m, 1H), 1.46-1.57 (m, 1H). FAB MS 555 (M+1).

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue partitioned between saturated NaHCO3 soln
  3. customThe layers were separated
  4. washthe organics were washed with H2O, brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customthe solvent removed in vacuo
  8. customto give an oil which
  9. customwas chromatographed on silica gel (3:97 MeOH:CH2Cl2)

Sources & evidence

ORD record
ord-8624c07f35114a9bbb47eccd0bf11b29
Source dataset
uspto-grants-1997_08
Patent number
US05661161

Reaction notes

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