4-Fluoroaniline → 6-oxo-3,4,5,6-tetrahydro-1H-azepino[5,4,3-cd]indole-2-carboxylic acid (4-fluoro-phenyl)-amide

HRID 33332Notes

Reaction equation

HRID 33332 reaction equation
[O:1]=[C:2]1[C:13]2[C:14]3[C:6](=[C:7]([C:15]([OH:17])=O)[NH:8][C:9]=3[CH:10]=[CH:11][CH:12]=2)[CH2:5][CH2:4][NH:3]1.[F:18][C:19]1[CH:25]=[CH:24][C:22]([NH2:23])=[CH:21][CH:20]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[F:18][C:19]1[CH:25]=[CH:24][C:22]([NH:23][C:15]([C:7]2[NH:8][C:9]3[CH:10]=[CH:11][CH:12]=[C:13]4[C:2](=[O:1])[NH:3][CH2:4][CH2:5][C:6]=2[C:14]=34)=[O:17])=[CH:21][CH:20]=1

Participants

5

Reactant 3

HCID 97314-FluoroanilineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 111281096-oxo-3,4,5,6-tetrahydro-1H-azepino[5,4,3-cd]indole-2-carboxylic acid

Product 1

HCID 183399766-oxo-3,4,5,6-tetrahydro-1H-azepino[5,4,3-cd]indole-2-carboxylic acid (4-fluoro-phenyl)-amide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

6-Oxo-3,4,5,6-tetrahydro-1H-azepino[5,4,3-cd]indole-2-carboxylic acid (100 mg, 0.43 mmol), 4-fluoroaniline (48 mg, 0.43 mmol), and diisoprophylethylamine (168 mg, 1.30 mmol) were dissolved in 5 mL dry DMF. HATU (173 mg, 0.46 mmol) was added and the resulting mixture stirred at room temperature under argon for 3 d. The reaction mixture was partitioned between water and 25% iPrOH/CHCl3. The layers were separated, and the aqueous layer extracted thrice with 25% iPrOH/CHCl3. The combined organic layers were dried (MgSO4) and concentrated in vacuo leaving an off-white solid which was recrystallized from chloroform/methanol to yield 6-oxo-3,4,5,6-tetrahydro-1H-azepino[5,4,3-cd]indole-2-carboxylic acid (4-fluoro-phenyl)-amide, 70 mg (50%) as a pale yellow solid: m.p. 330-332° C. (dec); 1H NMR (300 MHz, d6-DMSO) δ 3.28 (m, 2H), 3.42 (m, 2H), 7.22 (m, 2H), 7.35 (app t, J=7.8 Hz, 1H), 7.65 (dd, J=7.8, 0.6 Hz, 1H), 7.77 (m, 3H), 8.16 (br t, 1H), 10.08 (br s, 1H), 11.81 (br s, 1H). MS (electrospray, MH+) 324. Anal. (C18H14FN3O2.0.4 H2O) C, H, N.

Workup

  1. customThe reaction mixture was partitioned between water and 25% iPrOH/CHCl3
  2. customThe layers were separated
  3. extractionthe aqueous layer extracted thrice with 25% iPrOH/CHCl3
  4. dry with materialThe combined organic layers were dried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customleaving an off-white solid which
  7. customwas recrystallized from chloroform/methanol

Sources & evidence

ORD record
ord-8f976afe0e3b456984661a75f590d78d
Source dataset
uspto-grants-2008_09
Patent number
US07429578B2

Reaction notes

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