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 2216328Notes

Reaction equation

HRID 2216328 reaction equation
[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

Participants

7

Reactant 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

Product 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

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-1486e906a1664dd9b1922d7a0f71b115
Source dataset
uspto-grants-2006_09
Patent number
US07112583B2

Reaction notes

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