Triphenylphosphine → 2-Chloro-11-fluoro-5-methyl-5,6-dihydroindolo[2,1-a][2,6]naphthyridine

HRID 595721Notes

Reaction equation

HRID 595721 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH:8]([CH3:11])[CH2:9]O)=[C:4]([C:12]2[NH:13][C:14]3[C:19]([CH:20]=2)=[C:18]([F:21])[CH:17]=[CH:16][CH:15]=3)[CH:3]=1.CCOC(/N=N/C(OCC)=O)=O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>C1COCC1.O>[Cl:1][C:2]1[N:7]=[CH:6][C:5]2[CH:8]([CH3:11])[CH2:9][N:13]3[C:14]4[CH:15]=[CH:16][CH:17]=[C:18]([F:21])[C:19]=4[CH:20]=[C:12]3[C:4]=2[CH:3]=1

Participants

6

Reactant 3

HCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 903334522-(6-chloro-4-(4-fluoro-1H-indol-2-yl)pyridin-3-yl)propan-1-ol

Product 1

HCID 903339322-Chloro-11-fluoro-5-methyl-5,6-dihydroindolo[2,1-a][2,6]naphthyridineYield 56%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 2-(6-chloro-4-(4-fluoro-1H-indol-2-yl)pyridin-3-yl)propan-1-ol (60 mg, 0.21 mmol) and DEAD (111 mg, 0.63 mmol) in THF (4 mL) was added PPh3 (156 mg, 0.63 mmol) at 0° C. under N2, and the mixture was stirred for 12 hours. Then the mixture was diluted with H2O and extracted with EA. The combined organic layer was washed with H2O, brine, dried over Na2SO4, filtrated and concentrated to give 2-chloro-11-fluoro-5-methyl-5,6-dihydroindolo[2,1-a][2,6]naphthyridine (30 mg, yield: 56%). 1H-NMR (CDCl3, 400 MHz) δ 8.26 (s, 1H), 7.54 (s, 1H), 7.05˜7.15 (m, 3H), 6.73˜6.77 (m, 1H), 4.16˜4.20 (m, 1H), 4.00˜4.04 (m, 1H), 3.31˜3.35 (m, 1H), 1.30 (d, J=8.0 Hz, 3H). MS (M+H)+: 287/289.

Workup

  1. extractionextracted with EA
  2. washThe combined organic layer was washed with H2O, brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltrated
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-386637657d9e4263b6658344b4806235
Source dataset
uspto-grants-2016_01
Patent number
US09243002B2

Reaction notes

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