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

HRID 363205ノート

反応式

HRID 363205 の反応式
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

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

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) δ8.33 (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).

後処理

  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)

出典と根拠

ORDレコード
ord-2fa7ee4377d44a60ab4b8ce6ea6d1228
出典データセット
uspto-grants-1999_02
特許番号
US05872135

反応ノート

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