Dimethylformamide → HCID 77357100, compound

HRID 1655007Notes

Reaction equation

HRID 1655007 reaction equation
C([N:3]([CH2:6][CH3:7])[CH2:4][CH3:5])C.[NH2:8][C:9]1[CH:10]=[C:11]([C:15]2[C:16](=[O:22])[N:17]([CH3:21])[CH2:18][C:19]=2[OH:20])[CH:12]=[CH:13][CH:14]=1.[CH3:23][N:24]([CH3:27])[CH:25]=[O:26]>>[CH2:11]1[CH2:12][CH:5]([C:4]2([NH:17][C:16]([NH:8][C:9]3[CH:14]=[CH:13][CH:12]=[C:11]([C:15]4[C:16](=[O:22])[N:17]([CH3:21])[CH2:18][C:19]=4[OH:20])[CH:10]=3)=[O:22])[N:3]=[CH:6][C:7]3[CH:13]=[CH:14][CH:9]=[CH:10][C:23]=3[N:24]([CH3:27])[C:25]2=[O:26])[CH2:18][CH2:19][CH2:15]1

Participants

4

Reactant 3

HCID 6228Dimethylformamide2×HCID 8471TriethylamineHCID 54707315HCID 54707315, compound

Product 1

HCID 77357100HCID 77357100, compoundYield 30%

Conditions

Temperature
50 °C

Procedure

A solution of 5-cyclohexyl-l,3-dihydro-1-methyl-3(R,S)-[(4-nitrohenyloxycarbonyl)amino]-2H-1,4-benzodiazepin-2-one (Example 1, Step 9) (400 mg, 0.92 mmol) in anhydrous dimethylformamide (5.5 ml), under an atmosphere of nitrogen, at ambient temperature, was treated with triethylamine (126 μl 0.92 mmol). After stirring for 5 min, a solution of 3-(3-aminophenyl)-1,5-dihydro-4-hydroxy-N-methyl-2H-pyrrol-2-one (187 mg, 0.92 mmol) in anhydrous dimethylformamide (5.5 ml) was added dropwise. The solution was then heated at 50° C. for 2 h. The solution was cooled to room temperature and the solvent evaporated in vacuo. The residue was partitioned between ethyl acetate (20 ml) and 20% aqueous acetic acid (20 ml). The undissolved solid was filtered off and triturated with ether (20 ml) then hot methanol (20 ml), to afford the title compound (139 mg, 30%) as a white solid. mp 199°-201° C. 1H NMR (360MHz, D6 -DMSO) δ0.91 (1H, m), 1.09-1.93 (9H, m), 2.90 (4H, m), 3.31 (3H, s), 3.91 (2H, s), 5.07 (1H, d, J=8Hz), 7.13 (1H, t, J=8Hz), 7.23 (1H, d, J=8Hz), 7.36 (2H, m), 7.54 (2H, m), 7.63 (1H, m), 7.75 (1H, d, J=8Hz), 7.84 (1H, s), 8.96 (1H, s).

Workup

  1. temperatureThe solution was cooled to room temperature
  2. customthe solvent evaporated in vacuo
  3. customThe residue was partitioned between ethyl acetate (20 ml) and 20% aqueous acetic acid (20 ml)
  4. filtrationThe undissolved solid was filtered off
  5. customtriturated with ether (20 ml)

Sources & evidence

ORD record
ord-5e2a2f28bbd44ce7ba56adeaf3b22216
Source dataset
uspto-grants-1995_04
Patent number
US05410049

Reaction notes

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