Tetrahydrofuran → HCID 11707040, compound

HRID 1867628Notes

Reaction equation

HRID 1867628 reaction equation
[NH2:1][CH:2]1[N:8]=[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:6]2[CH:15]=[CH:16][CH:17]=[CH:18][C:5]=2[N:4]([CH2:19][C:20]([F:23])([F:22])[F:21])[C:3]1=[O:24].C(N(CC)CC)C.Cl.[C:33]1([C:39]2[NH:40][C:41](=[O:50])[N:42]([CH:44]3[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]3)[CH:43]=2)[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.[O:51]1CCC[CH2:52]1>>[O:24]=[C:3]1[C@H:2]([NH:1][C:52]([N:47]2[CH2:46][CH2:45][CH:44]([N:42]3[CH:43]=[C:39]([C:33]4[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=4)[NH:40][C:41]3=[O:50])[CH2:49][CH2:48]2)=[O:51])[N:8]=[C:7]([C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:6]2[CH:15]=[CH:16][CH:17]=[CH:18][C:5]=2[N:4]1[CH2:19][C:20]([F:21])([F:23])[F:22]

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 8471Triethylamine2×HCID 107353833-Amino-5-phenyl-1-(2,2,2-trifluoroethyl)-1H-benzo[e][1,4]diazepin-2(3H)-oneHCID 67344326HCID 67344326, compound

Product 1

HCID 11707040HCID 11707040, compound

Conditions

Temperature
0 °C

Procedure

3-Amino-2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-1,4-benzodiazepine (20.0 mg, 0.06 mmol) (Y.-J. Shi et al., Tetrahedron, 1999, 55, 909-918) and p-nitrophenylchloroformate (12.1 mg, 0.06 mmol) were dissolved in tetrahydrofuran (0.5 mL) under argon, and cooled to 0° C. Triethylamine (19 uL, 0.14 mmol) was added and the reaction stirred for 1 h, followed by addition of more triethylamine (19 uL) and 4-phenyl-1-piperidin-4-yl-1,3-dihydro-2H-imidazol-2-one hydrochloride (16.8 mg, 0.06 mmol), prepared according to the procedure described in the patent U.S. Pat. No. 6,344,449 B1. The reaction was warmed to room temperature and stirred overnight. The crude product was purified by reverse phase HPLC (C-18, 5% to 95% 0.1% trifluoroacetic acid/acetonitrile in 0.1% aqueous trifluoroacetic acid gradient elution) to give she title compound (26.1 mg). MS 603 (M+1)

Workup

  1. customprepared
  2. temperatureThe reaction was warmed to room temperature
  3. stirringstirred overnight
  4. customThe crude product was purified by reverse phase HPLC (C-18, 5% to 95% 0.1% trifluoroacetic acid/acetonitrile in 0.1% aqueous trifluoroacetic acid gradient elution)

Sources & evidence

ORD record
ord-6df4aa9ef2b249f191c80b9b40ddfb9b
Source dataset
uspto-grants-2009_12
Patent number
US07632832B2

Reaction notes

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