Triethylamine → 3-(2(R)-Cyclopentylmethyl-3 (S)-hydroxyl-1-oxo-5-phenylpentyl)amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one

HRID 30304Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 30304
[CH:1]1([CH2:6][C@H:7]([C@@H:11]([OH:20])[CH2:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:8]([OH:10])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.C1(C)C=CC(S(O)(=O)=O)=CC=1.[NH2:32][CH:33]1[N:39]=[C:38]([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[C:37]2[CH:46]=[CH:47][CH:48]=[CH:49][C:36]=2[N:35]([CH3:50])[C:34]1=[O:51].O.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C>C(Cl)Cl.C(OCC)(=O)C>[CH:1]1([CH2:6][C@H:7]([C@@H:11]([OH:20])[CH2:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:8]([NH:32][CH:33]2[N:39]=[C:38]([C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)[C:37]3[CH:46]=[CH:47][CH:48]=[CH:49][C:36]=3[N:35]([CH3:50])[C:34]2=[O:51])=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5]1

Komponenten

7

Edukt 4

HCID 8471TriethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 183467692(R)-cyclopentylmethyl-3(S)-hydroxyl-5-phenylpentanoic acidHCID 219414933-Amino-1-methyl-5-phenyl-2,3-dihydro-1h-1,4-benzodiazepin-2-one p-toluenesulfonate salt

Produkt 1

HCID 98930003-(2(R)-Cyclopentylmethyl-3 (S)-hydroxyl-1-oxo-5-phenylpentyl)amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

A mixture of acid 4 (250 mg, 0.900 mmol) and 3-amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one p-toluenesulfonate salt (364 mg, 0.820 mmol) in 4 mL of methylene chloride was stirred at 0° C. 1-Hydroxy-benzotriazole hydrate (133 mg, 0.980 mmol), 1-[3-(dimethylamine)propyl]-3-ethylcarbodiimide hydrochloride (314 mg, 1.64 mmol) and triethylamine (0.51 mL, 3.7 mmol) were added sequentially. After the mixture was stirred for 16 h, 30 mL of ethyl acetate was added. The organic layer was washed with 1 M HCl (15 mL), 5% NaHCO3 (30 mL) and brine (30 mL), dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Purification by chromatotron (30% ethyl acetate-hexane) afforded two diastereomers A and B. A: 120 mg (25%); 1H NMR (300 MHz, CDCl3) δ 7.20-7.70 (15H, m), 5.54 (1H, d, J=8.0 Hz), 4.02 (1H, m), 3.48 (3H, s), 2.83-3.00 (1H, m), 2.62-2.74 (1H, m), 2.40-2.48 (1H, m), 1.00-2.00 (13H, m); MS (ESI): 524 (M+H), 546 (M+Na), 522 (M−H), 558 (M+Cl). B: 120 mg (25%); 1H NMR (300 MHz, CDCl3) δ 7.60 (1H, d, J=6.9 Hz), 7.20-7.45 (14H, m), 5.56 (1H, d, J=8.4 Hz), 3.84 (1H, m), 3.48 (3H, s), 2.83-3.00 (1H, m), 2.62-2.74 (1H, m), 2.50-2.60 (1H, m), 1.00-1.95 (13H, m); MS (ESI): 524 (M+H), 546 (M+Na), 522 (M−H).

Aufarbeitung

  1. stirringAfter the mixture was stirred for 16 h
  2. washThe organic layer was washed with 1 M HCl (15 mL), 5% NaHCO3 (30 mL) and brine (30 mL)
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customPurification by chromatotron (30% ethyl acetate-hexane)
  6. customafforded two diastereomers A and B

Quellen und Nachweise

ORD-Eintrag
ord-c244e8262bfd41bdaf615b58baed7684
Quelldatensatz
uspto-grants-2008_09
Patentnummer
US07423033B2

Notizen zur Reaktion

Wird geladen…