Methyl iodide → 2-Methyl-5-(2-phenoxy-phenyl)-3-phenyl-1H-pyrrolo[2,3-b]pyridine

HRID 2114077Notes

Reaction equation

HRID 2114077 reaction equation
C1(S([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=4[O:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[CH:18]=C3C(C3C=CC=CC=3)=C2)(=O)=O)C=CC=CC=1.[C:38]([Li])([CH3:41])([CH3:40])[CH3:39].[CH3:43][CH2:44][CH2:45][CH2:46][CH3:47].[CH3:48]I>C1COCC1.CCOC(C)=O.C([O-])(O)=O.[Na+]>[CH3:48][C:39]1[NH:10][C:14]2=[N:15][CH:16]=[C:17]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[O:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH:18]=[C:40]2[C:38]=1[C:41]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1

Participants

8

Reactant 4

HCID 6328Methyl iodideHCID 8003PentaneHCID 67051395HCID 67051395, compoundHCID 178418306HCID 178418306, compound

Product 1

HCID 536302462-Methyl-5-(2-phenoxy-phenyl)-3-phenyl-1H-pyrrolo[2,3-b]pyridineYield 7.3%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a stirred and cooled (−78° C.) solution of the azaindole 28 (80 mg, 0.16 mmol) in dry THF (2 mL) was added a 1.5 M solution of tert-butyllithium in pentane (0.13 mL, 0.19 mmol) dropwise. After 0.6 h, methyl iodide (0.10 mL, 1.61 mmol) was added dropwise and the reaction mixture allowed to slowly warm to room temperature. Following a further 22.5 h the mixture was diluted with EtOAc and saturated NaHCO3 solution and partitioned. The aqueous layer was washed with EtOAc (3×). The combined organic extracts were dried (MgSO4), filtered and concentrated. The product was purified by PTLC using hexanes-EtOAc=4:1 as eluent to afford the desired azaindole 63 (4.4 mg, 7.3%). 1H NMR (400 MHz; CDCl3) δ 3.94 (s, 3H), 6.93-6.96 (m, 2H), 7.01-7.05 (m, 1H), 7.08 (dd, J=1.3 and 8.1 Hz, 1H), 7.22-7.29 (m, 3H), 7.33-7.39 (m, 4H), 7.50-7.54 (m, 3H), 8.35 (d, J=2.0 Hz, 1H) and 8.57 (d, J=2.0 Hz, 1H). MS (CI) m/z 377 (MH+).

Workup

  1. waitFollowing a further 22.5 h
  2. custompartitioned
  3. washThe aqueous layer was washed with EtOAc (3×)
  4. dry with materialThe combined organic extracts were dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe product was purified by PTLC

Sources & evidence

ORD record
ord-8c9ba651014a4af1a3fb317a7d2578f5
Source dataset
uspto-grants-2008_10
Patent number
US07432375B2

Reaction notes

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