Acetic Acid → HCID 22396564, compound

HRID 1370382Notes

Reaction equation

HRID 1370382 reaction equation
[Br:1][C:2]1[C:3]2[C:4]3[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15][C:5]=3[N:6]([CH2:11][C:12](O)=O)[C:7]=2[CH:8]=[CH:9][CH:10]=1.C(N(CC)CC)C.ClC(OCC(C)C)=O.[C:42]1([NH2:49])[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=1[NH2:48].C(O)(=O)C>C1COCC1.CCOC(C)=O>[NH:48]1[C:43]2[CH:44]=[CH:45][CH:46]=[CH:47][C:42]=2[N:49]=[C:12]1[CH2:11][N:6]1[C:7]2[CH:8]=[CH:9][CH:10]=[C:2]([Br:1])[C:3]=2[C:4]2[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15][C:5]1=2

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 7243O-PhenylenediamineHCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 22396652HCID 22396652, compound

Product 1

HCID 22396564HCID 22396564, compoundYield 59%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

A solution of (10-bromo-3-(tert-butoxycarbonyl)-2,3,4,5-tetrahydroazepino[4,5-b]indol-6(1H)-yl)acetic acid (0.152 g, 0.359 mmol) and triethylamine (0.052 mL, 0.038 g, 0.372 mmol, 1.04 equiv.) in THF (2 mL) was cooled to 0° C. under N2. Isobutyl chloroformate (0.048 mL, 0.051 g, 0.372 mmol, 1.04 equiv.) was added and the reaction mixture was stirred for 2.3 h. o-Phenylenediamine (0.0406 g, 0.375 mmol, 1.04 equiv.) and acetic acid (0.24 mL, 0.26 g, 4.25 mmol, 11.8 equiv.) were added, and the reaction mixture was heated to 50° C. The temperature of the reaction mixture gradually was increased to 64° C. over 3 h. After 19 h, the reaction mixture was cooled to rt. The reaction mixture was taken up in EtOAc, and the resulting solution was washed with water, saturated aq. NaHCO3, and brine. The organic layer was dried over MgSO4, filtered and concentrated. The crude product (0.1865 g) was chromatographed (SiO2 22 g, eluted with 5:1 toluene:acetone) to give tert-butyl 6-(1H-benzimidazol-2-ylmethyl)-10-bromo-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate (0.105 g) in 59% yield. 1H NMR (300 MHz, CDCl3) δ 1.12, 3.20, 3.54, 3.68-3.74, 5.54, 5.58, 6.88, 7.20, 7.23-7.30.

Workup

  1. additionwere added
  2. temperatureThe temperature of the reaction mixture gradually was increased to 64° C. over 3 h
  3. temperaturethe reaction mixture was cooled to rt
  4. washthe resulting solution was washed with water, saturated aq. NaHCO3, and brine
  5. dry with materialThe organic layer was dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product (0.1865 g) was chromatographed
  9. wash(SiO2 22 g, eluted with 5:1 toluene:acetone)

Sources & evidence

ORD record
ord-b44fcd53fbf94c639607e85280d2201f
Source dataset
uspto-grants-2003_06
Patent number
US06583135B2

Reaction notes

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