Hydrochloric Acid → t-Butyl 4-[9-(benzoylamino)-6,10-dioxo-1,2,3,4,7,8,9,10-octahydro-6H-pyridazino-[1,2-a][1,2]diazepine-1-carboxamido]-5-oxopentanoate

HRID 1532897Notes

Reaction equation

HRID 1532897 reaction equation
[C:1]([NH:9][CH:10]1[C:16](=[O:17])[N:15]2[CH:18]([C:22]([NH:24][CH:25]([CH:39]=[O:40])[CH2:26][CH2:27][C:28](=NNC(N)=O)[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:23])[CH2:19][CH2:20][CH2:21][N:14]2[C:13](=[O:41])[CH2:12][CH2:11]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C=[O:43].Cl>CO>[C:1]([NH:9][CH:10]1[C:16](=[O:17])[N:15]2[CH:18]([C:22]([NH:24][CH:25]([CH:39]=[O:40])[CH2:26][CH2:27][C:28]([O:29][C:30]([CH3:32])([CH3:33])[CH3:31])=[O:43])=[O:23])[CH2:19][CH2:20][CH2:21][N:14]2[C:13](=[O:41])[CH2:12][CH2:11]1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 53703560t-Butyl 4-[9-(benzoylamino)-6,10-dioxo-1,2,3,4,7,8,9,10-octahydro-6H-pyridazino-[1,2-a][1,2]diazepine-1-carboxamido]-5-oxopentanoate semicarbazone

Product 1

HCID 54215480t-Butyl 4-[9-(benzoylamino)-6,10-dioxo-1,2,3,4,7,8,9,10-octahydro-6H-pyridazino-[1,2-a][1,2]diazepine-1-carboxamido]-5-oxopentanoateYield 51%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of semicarbazone 233e (390 mg, 0.68 mmol) in methanol (10 ml) was cooled at 0° C. and then treated with a 38% aq. solution of formaldehyde (2 ml) and 1M HCl (2 ml). The reaction mixture was then stirred overnight at room temperature. The solution was concentrated to remove the methanol. The aq. solution was extracted with EtOAc (30 ml). The organic solution was successively washed with 10% NaHCO3 (30 ml) and sat. aq. NaCl (30 ml), dried (MgSO4) and concentrated. Purification by flash chromatography on silica gel (2-5% methanol in CH2Cl2) afforded 234e (179 mg, 51%) as a white foam: [α]D20 −101° (c 0.064, MeOH); IR (KBr)3346, 2976, 2934, 1730, 1657, 1535, 1456, 1425, 1278, 1255, 1156, 708; 1H NMR (CDCl3) δ 9.56 (1H, s), 7.88-7.38 (5H, m), 7.01 and 6.92 (2H, 2d), 5.27-5.08 (2H, m), 4.69-4.46 (1H, m), 3.50-3.27 (2H, m), 3.15-2.73 (2H, m), 2.46-1.83 (10H, m), 1.45 (9H, s).

Workup

  1. concentrationThe solution was concentrated
  2. customto remove the methanol
  3. extractionThe aq. solution was extracted with EtOAc (30 ml)
  4. washThe organic solution was successively washed with 10% NaHCO3 (30 ml) and sat. aq. NaCl (30 ml)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. customPurification by flash chromatography on silica gel (2-5% methanol in CH2Cl2)

Sources & evidence

ORD record
ord-c47de99236d74c33ac02a59c0d1a72ec
Source dataset
uspto-grants-2001_03
Patent number
US06204261B1

Reaction notes

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