Pyridine → 3-Benzyl-10-methoxy-1,2,3,4,4a,5-hexahydrobenzo[b]pyrazino[1,2-d][1,4]diazepin-6(7h)-one

HRID 1035275Notes

Reaction equation

HRID 1035275 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[N:10]1[CH2:15][CH2:14]N(CC2C=CC=CC=2)[CH2:12][CH:11]1[CH2:23][C:24]([OH:26])=O.[N:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.Cl.CN(C)[CH2:36][CH2:37]CN=C=NCC>CN(C)C=O>[CH2:32]([N:27]1[CH2:14][CH2:15][N:10]2[C:3]3[CH:4]=[C:5]([O:8][CH3:9])[CH:6]=[CH:7][C:2]=3[NH:1][C:24](=[O:26])[CH2:23][CH:11]2[CH2:12]1)[C:31]1[CH:37]=[CH:36][CH:28]=[CH:29][CH:30]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 667697652-(1-(2-Amino-5-methoxyphenyl)-4-benzylpiperazin-2-yl)acetic acid

Product 1

HCID 667698133-Benzyl-10-methoxy-1,2,3,4,4a,5-hexahydrobenzo[b]pyrazino[1,2-d][1,4]diazepin-6(7h)-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of Example 12E (0.390 g, 1.097 mmol) in N,N-dimethylformamide (3.66 mL) were added pyridine (4.44 mL, 54.9 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.421 g, 2.195 mmol) and the mixture was stirred at room temperature for 1 hour. The solution was concentrated, water was added to the residue, and the product was extracted twice with ethyl acetate. The combined organic washes were dried over sodium sulfate, concentrated and dried under vacuum at room temperature overnight. It was then passed through a 5 gram silica gel cartridge eluting first with dichloromethane, then with 2% methanol/dichloromethane and finally with 5% methanol/dichloromethane to obtain the title compound. An aliquot of material was further purified for analytical purposes by preparative HPLC to afford the title compound as the trifluoroacetic acid salt. 1H NMR (500 MHz, DMSO-d6) δ ppm 10.21 (s, 1H), 9.52 (s, 1H), 7.54-7.48 (m, 5H), 6.90 (d, J=8.6, 1H), 6.70-6.60 (m, 2H), 4.45 (s, 2H), 3.74 (s, 3H), 3.67-3.07 (m, 7H), 3.22-3.04 (m, 2H), 2.61 (dd, J=7.0, 13.5, 1H), 2.00 (d, J=13.5, 1H); MS (ESI) m/z 338.1 (M+H)+.

Workup

  1. concentrationThe solution was concentrated
  2. additionwater was added to the residue
  3. extractionthe product was extracted twice with ethyl acetate
  4. dry with materialThe combined organic washes were dried over sodium sulfate
  5. concentrationconcentrated
  6. customdried under vacuum at room temperature overnight
  7. washeluting first with dichloromethane

Sources & evidence

ORD record
ord-8501152a987a477fad4c20376da72b68
Source dataset
uspto-grants-2013_10
Patent number
US08546377B2

Reaction notes

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