Trifluoroacetic acid → 2-[2,4-Dioxo-5-phenyl-3-methyl-3-(3-carboxyphenyl)carbamoylmethyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-isopropyl-N-phenyl acetamide

HRID 343190

Reaction equation

HRID 343190 reaction equation
C([C:4](C1C=CC=CC=1)([C:29](=[O:31])[NH2:30])[N:5]1[C:11](=[O:12])[C:10]([CH2:14]C(O)=O)([CH3:13])[C:9](=[O:18])[N:8]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:7]2[CH:25]=[CH:26][CH:27]=[CH:28][C:6]1=2)(C)C.C(OC(CC1(CC(O)=O)[C:55](=[O:56])[N:54](C(C(C)C)(C2C=CC(OC)=CC=2)C(=O)N)[C:53]2[CH:72]=[CH:73][CH:74]=[CH:75][C:52]=2N(C2C=CC=CC=2)C1=O)=O)C1C=CC=CC=1.N[C:88]1[CH:89]=[C:90]([CH:98]=[CH:99][CH:100]=1)C(OC(C)(C)C)=O.[CH2:101]1[CH2:105]N([P+](Br)(N2CCCC2)N2CCCC2)C[CH2:102]1.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.[C:134]([OH:140])(C(F)(F)F)=[O:135]>CN(C=O)C.O>[O:12]=[C:11]1[N:5]([CH2:4][C:29]([N:30]([CH:101]([CH3:105])[CH3:102])[C:90]2[CH:98]=[CH:99][CH:100]=[CH:88][CH:89]=2)=[O:31])[C:6]2[CH:28]=[CH:27][CH:26]=[CH:25][C:7]=2[N:8]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:9](=[O:18])[C:10]1([CH3:13])[CH2:14][C:55](=[O:56])[NH:54][C:53]1[CH:52]=[CH:75][CH:74]=[C:73]([C:134]([OH:140])=[O:135])[CH:72]=1

Participants

9

Reactant 6

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 2737408tert-Butyl-3-aminobenzoateHCID 67696769[1-(isopropyl-phenyl-carbamoylmethyl)-3-methyl-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl]acetic acidHCID 86753587{3-(Benzyloxycarbonyl-methyl)-1-[isopropyl-(4-methoxy-phenyl)-carbamoylmethyl]-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl}acetic acid

Product 1

HCID 676965212-[2,4-Dioxo-5-phenyl-3-methyl-3-(3-carboxyphenyl)carbamoylmethyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-isopropyl-N-phenyl acetamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

A solution of 0.19 g (0.38 mmol) of [1-(isopropyl-phenyl-carbamoylmethyl)-3-methyl-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl]acetic acid, prepared as in Intermediate 7, 0.15 g (0.76 mmol) of t-butyl 3-aminobenzoate, 0.35 g (0.76 mmol) of PyBrOP and 0.27 mL (1.5 mmol) of N,N-diisopropyl-N-ethylamine in 2 mL of DMF is stirred at 50° C. for 17 h. The reaction mixture is diluted with 30 mL of H2O and extracted with EtOAc (×3). The organic extract is washed with H2O, 1N HCl, and brine, dried over MgSO4 and concentrated in vacuo to a brown foam. The crude product is dissolved in 2 mL of CH2Cl2 and 0.3 mL (3.8 mmol) of TFA added. After stirring at RT for 1 d, the reaction mixture is concentrated in vacuo to a brown oil. Purification by reverse phase C-18 MPLC (60-80% methanol/TFA-H2O) gave 99 mg of the title compound as a white powder: 1H NMR (CDCl3 300 MHz, mixture of conformations) δ8.8-6.8 (m, 20H), 5.07 (m, 1H), 4.78 (d, 1H, J=12), 3.79 (d, 1H, J=12), 2.70 (q, 2H, J=10), 1.70 (s, 3H), 1.09 (m, 6H); low resolution MS (FAB) m/e 619 (MH+); Anal. (C36H34N4O6.0.75 TFA.H2O) Calc. C, 62.4; H, 5.1; N, 7.8; Found: C, 62.4; H, 5.2; N, 7.7.

Workup

  1. extractionextracted with EtOAc (×3)
  2. extractionThe organic extract
  3. washis washed with H2O, 1N HCl, and brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo to a brown foam
  6. dissolutionThe crude product is dissolved in 2 mL of CH2Cl2
  7. stirringAfter stirring at RT for 1 d
  8. concentrationthe reaction mixture is concentrated in vacuo to a brown oil
  9. customPurification by reverse phase C-18 MPLC (60-80% methanol/TFA-H2O)

Sources & evidence

ORD record
ord-e58534067c2c4cf39df2576beb9500a6
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Linked notes

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