Tetrahydrofuran → N-((3R,6S)-1-(cyclopropylmethyl)-2-oxo-6-phenylazepan-3-yl)-4-(5-oxo-3-phenyl-4,5-dihydro-1,2,4-triazol-1-yl)piperidine-1-carboxamide

HRID 1725658Notes

Reaction equation

HRID 1725658 reaction equation
C(N(CC)CC)C.[NH2:8][C@@H:9]1[CH2:15][CH2:14][C@@H:13]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:12][N:11]([CH2:22][CH:23]2[CH2:25][CH2:24]2)[C:10]1=[O:26].ClC(O[C:31]1[CH:36]=[CH:35][C:34]([N+:37]([O-])=O)=C[CH:32]=1)=O.C(N(C(C)C)CC)(C)C.Cl.[C:50]1([CH:56]2[N:60](C3CCNCC3)[NH:59][C:58](=[O:67])[NH:57]2)[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1.[O:68]1CCC[CH2:69]1>ClCCl>[CH:23]1([CH2:22][N:11]2[CH2:12][C@H:13]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH2:14][CH2:15][C@@H:9]([NH:8][C:69]([N:37]3[CH2:32][CH2:31][CH:36]([N:59]4[C:58](=[O:67])[NH:57][C:56]([C:50]5[CH:51]=[CH:52][CH:53]=[CH:54][CH:55]=5)=[N:60]4)[CH2:35][CH2:34]3)=[O:68])[C:10]2=[O:26])[CH2:25][CH2:24]1

Participants

8

Reactant 6

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 81531DiisopropylethylamineHCID 821294-Nitrophenyl chloroformateHCID 58844837(3R,6S)-3-amino-1-(cyclopropylmethyl)-6-phenylazepan-2-oneHCID 671711335-phenyl-1-piperidin-4-yl-2,4-dihydro-3H-1,2,4-triazol-3-one hydrochloride

Product 1

HCID 135440450N-((3R,6S)-1-(cyclopropylmethyl)-2-oxo-6-phenylazepan-3-yl)-4-(5-oxo-3-phenyl-4,5-dihydro-1,2,4-triazol-1-yl)piperidine-1-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Triethylamine (0.006 mL, 0.035 mmol) was added to a solution of (3R,6S)-3-amino-1-(cyclopropylmethyl)-6-phenylazepan-2-one (9 mg, 0.035 mmol) and p-nitrophenyl chloroformate (7 mg, 0.035 mmol) in tetrahydrofuran (0.500 mL) at 0° C. After 0.5 h, diisopropylethylamine (0.027 mL, 0.14 mmol), 5-phenyl-1-piperidin-4-yl-2,4-dihydro-3H-1,2,4-triazol-3-one hydrochloride (9 mg, 0.035 mmol), and dichloromethane (0.500 mL) were added and the mixture was heated to reflux. After 2 h, the mixture was concentrated. Purification by reverse phase HPLC (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.1% trifluoroacetic acid) gave the title compound. MS 529.3 (M+1).

Workup

  1. temperaturethe mixture was heated to reflux
  2. waitAfter 2 h
  3. concentrationthe mixture was concentrated
  4. customPurification by reverse phase HPLC (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-6a82663218f340a39cf05ddab34f9518
Source dataset
uspto-grants-2009_02
Patent number
US07491713B2

Reaction notes

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