Trifluoroacetic acid → HCID 59594380, compound

HRID 2263685Notes

Reaction equation

HRID 2263685 reaction equation
[Br:1][C:2]1[CH:35]=[CH:34][CH:33]=[CH:32][C:3]=1[CH2:4][CH:5]1[C:11](=[O:12])[NH:10][C:9]2[CH:13]=[CH:14][C:15]([Cl:17])=[CH:16][C:8]=2[C:7]([C:18]2[CH:23]=[CH:22][C:21]([NH:24]C(=O)OC(C)(C)C)=[CH:20][CH:19]=2)=[N:6]1.FC(F)(F)C(O)=O.[OH-].[Na+]>ClCCl.O>[NH2:24][C:21]1[CH:20]=[CH:19][C:18]([C:7]2[C:8]3[CH:16]=[C:15]([Cl:17])[CH:14]=[CH:13][C:9]=3[NH:10][C:11](=[O:12])[CH:5]([CH2:4][C:3]3[CH:32]=[CH:33][CH:34]=[CH:35][C:2]=3[Br:1])[N:6]=2)=[CH:23][CH:22]=1

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 59594401HCID 59594401, compound

Product 1

HCID 59594380HCID 59594380, compoundYield 87%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (Z)-tert-butyl 4-(3-(2-bromobenzyl)-7-chloro-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-5-yl)phenylcarbamate (3.3 g, 5.94 mmol) in dichloromethane (45 mL) was added dropwise at 0° C. trifluoroacetic acid (15 mL). After completion of the addition, the reaction mixture was stirred at 0° C. for 1 h then the temperature was raised to room temperature and kept at room temperature for 4 h. The reaction mixture was cooled down to 0° C. and treated with a solution of 10% NaOH in water until a pH>10 was obtained. The two layers were separated. The aqueous layer was extracted with dichloromethane (2×50 mL). The combined extracts were washed with brine (100 mL), dried (MgSO4) and evaporated in vacuo. The crude material was purified by flash column chromatography (eluted with 40% EtOAc in Hexane) to give (Z)-5-(4-aminophenyl)-3-(2-bromobenzyl)-7-chloro-1H-benzo[e][1,4]diazepin-2(3H)-one (2.35 g, 87%) as a pale yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 3.45 (d, 2H), 3.71 (t, 1H), 5.62 (s, 2H), 6.53 (d, 2H), 7.10-7.17 (m, 3H), 7.22-7.25 (m, 2H), 7.33 (t, 1H), 7.46-7.61 (m, 3H), 10.64 (s, 1H). MS, m/z 455.19 [M+1]. Part V: Installation of Urea from C5-Aminoaryl Intermediate.

Workup

  1. additionAfter completion of the addition
  2. temperaturethe temperature was raised to room temperature
  3. waitkept at room temperature for 4 h
  4. temperatureThe reaction mixture was cooled down to 0° C.
  5. customwas obtained
  6. customThe two layers were separated
  7. extractionThe aqueous layer was extracted with dichloromethane (2×50 mL)
  8. washThe combined extracts were washed with brine (100 mL)
  9. dry with materialdried (MgSO4)
  10. customevaporated in vacuo
  11. customThe crude material was purified by flash column chromatography (eluted with 40% EtOAc in Hexane)

Sources & evidence

ORD record
ord-0f56101809ec4a35b40ce738d04c8875
Source dataset
uspto-grants-2010_12
Patent number
US07851465B2

Reaction notes

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