Trifluoroacetic acid → HCID 70181791, compound

HRID 264024Notes

Reaction equation

HRID 264024 reaction equation
C([O:5][C:6](=[O:52])[CH2:7][N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:10]=[C:9]1[C:17](=[O:51])[NH:18][CH:19]1[C:25](=[O:26])[N:24]([C:27]([CH:37]([CH3:39])[CH3:38])([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[C:28](=[O:30])[NH2:29])[C:23]2[CH:40]=[CH:41][CH:42]=[CH:43][C:22]=2[N:21]([C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[C:20]1=[O:50])(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[CH:37]([C:27]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)([C:28](=[O:30])[NH2:29])[N:24]1[C:25](=[O:26])[CH:19]([NH:18][C:17]([C:9]2[N:8]([CH2:7][C:6]([OH:52])=[O:5])[C:16]3[C:11]([CH:10]=2)=[CH:12][CH:13]=[CH:14][CH:15]=3)=[O:51])[C:20](=[O:50])[N:21]([C:44]2[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=2)[C:22]2[CH:43]=[CH:42][CH:41]=[CH:40][C:23]1=2)([CH3:39])[CH3:38]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 70181742HCID 70181742, compound

Product 1

HCID 70181791HCID 70181791, compoundYield 75.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of {2-[1 -(Isopropyl-phenyl-carbamoylmethyl)-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-1 H-benzo[b][1,4]diazepin-3-ylcarbamoyl]-indol-1-yl}-acetic acid tert-butyl ester (0.072 g) in dichloromethane (4 ml) at ambient temperature was added trifluoroacetic acid (1.5 ml) gradually with stirring. After the reaction was stirred 30 minutes, the dichloromethane and trifluoroacetic acid were evaporated under reduced pressure to afford a clear glass. The glass was purified by purified RP-HPLC on a C-18 column with a gradient elution of 45-55% acetonitrile in water with 0.1% trifluoroacetic acid buffer over a 30 minute period at a rate of 100 ml/min. Fractions containing the desired material were combined, frozen and lyophilized to afford the title compound (0.050 g) as a white powder. 1H NMR (300 MHz, CDCl3): d 1.07 (d, J=4.4 Hz, 3H), 1.10 (d, J=4.4 Hz, 3H), 4.23 (d, J=16.6 Hz, 1H), 4.40 (d, J=16.6 Hz, 1H), 5.01 (m, 1H), 5.06 (s, 2H), 5.44 (d, J=7.1 Hz, 1H), 7.03 (dd, J=1.2, 8.1 Hz, 1H), 7.17-7.52 (m, 17H), 7.67 (d, J=8.1 Hz, 1H), 7.74 (d, J=7.1 Hz, 1H); MS (ES): m/z=644.2 (MH+); TLC (CH2Cl2 /CH3OH(19:1)): Rf =0.15; RP-HPLC (Vydac C-18, 25 cm×4.6 mm; 45-55% CH3CN in H2O with 0.1% TFA buffer;, 30 minutes; 1 ml/min): tf =22 min (to =3 min).

Workup

  1. stirringAfter the reaction was stirred 30 minutes
  2. customthe dichloromethane and trifluoroacetic acid were evaporated under reduced pressure
  3. customto afford a clear glass
  4. customThe glass was purified
  5. customby purified RP-HPLC on a C-18 column
  6. washwith a gradient elution of 45-55% acetonitrile in water with 0.1% trifluoroacetic acid buffer over a 30 minute period at a rate of 100 ml/min
  7. additionFractions containing the desired material
  8. temperaturefrozen

Sources & evidence

ORD record
ord-47c087ca76764d269c0640c1eabf8e80
Source dataset
uspto-grants-1997_07
Patent number
US05646140

Reaction notes

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