Phosphorus trichloride → HCID 136342132, compound

HRID 748546Notes

Reaction equation

HRID 748546 reaction equation
[N:1]1([CH2:7][C:8]2[CH:9]=[CH:10][C:11]([C:15]3[C:23]4[C:18](=[CH:19][CH:20]=[C:21]([C:24]5[CH:25]=[N:26][CH:27]=[CH:28][CH:29]=5)[CH:22]=4)[NH:17][C:16]=3[OH:30])=[N+:12]([O-])[CH:13]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.P(Cl)(Cl)Cl>C(OCC)(=O)C>[N:1]1([CH2:7][C:8]2[CH:9]=[CH:10][C:11]([C:15]3[C:23]4[C:18](=[CH:19][CH:20]=[C:21]([C:24]5[CH:25]=[N:26][CH:27]=[CH:28][CH:29]=5)[CH:22]=4)[NH:17][C:16]=3[OH:30])=[N:12][CH:13]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 24387Phosphorus trichlorideHCID 178526264HCID 178526264, compound

Product 1

HCID 136342132HCID 136342132, compoundYield 3%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of 3-[5-(morpholin-4-ylmethyl)-1-oxidopyridin-2-yl]-5-pyridin-3-yl-1H-indol-2-ol (200 mg, 0.6 mmol) in ethyl acetate (60 mL) was added phosphorus trichloride (0.4 mL). A yellow precipitate was formed and the mixture was refluxed for 3 h, and then diluted with ethyl acetate and washed with an aqueous saturated NaHCO3 solution. The aqueos layer was extracted with two portions of ethyl acetate and one portion of chloroform. The organic- layers were combined, dried (Na2SO4) and concentrated in vacuo. The crude product was purified by preparative HPLC (column: Xterra, 19×300 mm, eluent: water/acetonitrile, (0:100 to 100:0), gradient) affording 6 mg (3% yield) of the title compound as a yellow solid: 1H NMR (DMSO-d6, 400 MHz) δ 10.50 (br s, 1 H), 8.92 (d, J=2 Hz, 1 H), 8.49 (dd, J=4, 1 Hz, 1 H), 8.12-8.06 (m, 1 H), 8.02 (s, 1 H), 7.90-7.71 (m, 1 H), 7.71-7.67 (m, 2 H), 7.43 (dd, J=8, 5 Hz, 1 H), 7.20 (d, J=8 Hz, 1 H), 6.98 (d, J=8 Hz, 1 H), 3.63-3.53 (m, 4 H), 3.40-3.24 (m, 2 H), 2.42-2.34 (m, 4 H); MS (ES) m/z 388 (M++1).

Workup

  1. customA yellow precipitate was formed
  2. temperaturethe mixture was refluxed for 3 h
  3. washwashed with an aqueous saturated NaHCO3 solution
  4. extractionThe aqueos layer was extracted with two portions of ethyl acetate and one portion of chloroform
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by preparative HPLC (column: Xterra, 19×300 mm, eluent: water/acetonitrile, (0:100 to 100:0), gradient)

Sources & evidence

ORD record
ord-e81045956a1e4801a2658f06a660e5d8
Source dataset
uspto-grants-2008_07
Patent number
US07399780B2

Reaction notes

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