HCID 18468955, compound → HCID 57097216, compound

HRID 1871692Notes

Reaction equation

HRID 1871692 reaction equation
[CH3:1][C:2]1[C:6]2[N:7]=[CH:8][N:9]([CH2:12][C:13]([NH:15][CH:16]3[CH2:20][C:19](=[O:21])[O:18][CH:17]3[O:22]CC3C=CC=CC=3)=[O:14])[C:10](=[O:11])[C:5]=2[NH:4][CH:3]=1>CO.[Pd]>[CH3:1][C:2]1[C:6]2[N:7]=[CH:8][N:9]([CH2:12][C:13]([NH:15][C@H:16]([CH:17]=[O:22])[CH2:20][C:19]([OH:21])=[O:18])=[O:14])[C:10](=[O:11])[C:5]=2[NH:4][CH:3]=1

Participants

4

Reactant 1

HCID 18468955HCID 18468955, compound

Product 1

HCID 57097216HCID 57097216, compoundYield 78.2%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A mixture of 42 (131 mg, 0.33 mmol), in methanol (50 ml) and 10% palladium on carbon (100 mg) was stirred vigorously under an atmosphere of hydrogen for 2 h. An additional quantity of catalyst (100 mg) was added and the mixture hydrogenated for a further 2 h. The mixture was filtered through a 0.2 μM nylon membrane, and concentrated. The residue was recrystallized from methanol/diethyl ether to afford 79 mg (78%) of 43 as a hygroscopic white solid: mp. 222-226° C.; (decomp.); [α]D32 +0.5 (c 0.02, MeOH); IR (KBr) 3282, 1680, 1558, 1425 1275; 1H NMR (CD3OD) δ 8.03 (1H, s), 7.18 (1H, d, J=0.7), 4.79-4.74 (2H, m), 4.63-4.59 (1H, 2×d, J=3.6), 4.36-4.25 (1H, m), 2.78-2.39 (2H, m), 2.24 (3H, d, J=0.7). Anal. Calcd for C13H14N4O5. 1.4H2O: C, 47.10; H, 5.12; N, 16.90. Found: C, 47.00; H, 4.79; N, 16.59. FABMS m/e 307, 306 (M+), 244, 207, 190, 152, 115 (100%) ##STR130## (1S,9S) t-Butyl 6,10-dioxo-octahydro-9-(3-phenylpropionylamino)-6H-pyridazino [1,2-a] [1,2]diazepine-1-carboxylate (44a). To a solution of (1S,9S)t-butyl 9-amino-6,10-dioxo-octahydro-6H-pyridazino [1,2-a][1,2]diazepine-1-carboxylate (690 mg; 2.32 mmol; GB 2128984) in dioxane (16 ml) and water (4 ml) at 0° C. was added solid sodium bicarbonate (292 mg; 3.48 mmol) followed by dropwise addition of 3-phenylpropionyl chloride (470 mg; 2.78 mmol). The mixture was stirred at room temperature for 2 h then more sodium bicarbonate (200 mg; 2.38 mmol) and 3-phenylpropionyl chloride (100 mg; 0.6 mmol) was added. The mixture was stirred for a further 2 h at room temperature, diluted with ethyl acetate (50 ml), washed with saturated sodium bicarbonate (2×25 ml) then dried (MgSO4) and concentrated. The residue was purified by flash chromatography (0-50% ethyl acetate/chloroform) and finally crystallized by trituration with ether to afford 860 mg (86%) of a white solid: mp. 137-138° C.; [α]D23 -95.1° (c 0.549, CH2Cl2); IR (KBr) 3327, 1736, 1677, 1664, 1536, 1422, 1156; 1H NMR (CDCl3) δ 7.24 (5H, m), 6.50 (1H, d, J=7.5), 5.24 (1H, m), 4.90 (1H, m), 4.60 (1H, m), 3.44 (IR, m), 2.93 (2H, m), 2.84 (1H, m), 2.64 (1H, m), 2.54 (2H, m), 2.26 (2H, m), 1.70 (4H, m), 1.70 (9H, s). MS(FAB, m/z): 430 (M+ +1), 374, 242, 105, 91.

Workup

  1. filtrationThe mixture was filtered through a 0.2 μM nylon membrane
  2. concentrationconcentrated
  3. customThe residue was recrystallized from methanol/diethyl ether

Sources & evidence

ORD record
ord-b952f73f04cf47b9ac366301668614c9
Source dataset
uspto-grants-2000_08
Patent number
US06103711

Reaction notes

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