Phosphorus trichloride → HCID 135423329, compound

HRID 2245561Notes

Reaction equation

HRID 2245561 reaction equation
[H-].[Na+].[CH3:3][O:4][CH2:5][CH2:6][NH:7][C:8]([C:10]1[CH:11]=[C:12]2[C:16](=[CH:17][CH:18]=1)[NH:15][C:14](=[O:19])[CH2:13]2)=[O:9].[Cl:20][C:21]1[N+:26]([O-])=[CH:25][C:24]([CH2:28][N:29]2[CH2:34][CH2:33][O:32][CH2:31][CH2:30]2)=[CH:23][CH:22]=1.P(Cl)(Cl)Cl>CN(C)C=O>[ClH:20].[OH:19][C:14]1[NH:15][C:16]2[C:12]([C:13]=1[C:21]1[CH:22]=[CH:23][C:24]([CH2:28][N:29]3[CH2:34][CH2:33][O:32][CH2:31][CH2:30]3)=[CH:25][N:26]=1)=[CH:11][C:10]([C:8]([NH:7][CH2:6][CH2:5][O:4][CH3:3])=[O:9])=[CH:18][CH:17]=2

Participants

6

Reactant 4

HCID 24387Phosphorus trichlorideHCID 24758Sodium hydrideHCID 68544478HCID 68544478, compoundHCID 85873132HCID 85873132, compound

Product 1

HCID 135423329HCID 135423329, compoundYield 24%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of sodium hydride (97%, 0.030 g, 1.25 mmol) in N,N-dimethylformamide (1.5 mL) was added N-(2-methoxyethyl)-2-oxoindoline-5-carboxamide (0.176 g, 0.75 mmol). The formed mixture was stirred for 5 min at room temperature followed by the addition of 4-[(6-chloro-1-oxidopyridin-3-yl)methyl]morpholine (0.114 g, 0.5 mmol). The resulting reaction mixture was set under an N2 atmosphere and stirred for 1 h at 120° C. and then concentrated in vacuo. The remaining N,N-dimethylformamide was removed by co-evaporation with toluene (1×). The residue was purified on a silica gel column using chloroform/methanol/triethylamine, (90:10:1), as the eluent. The material was dissolved in chloroform (4 mL), and phosphorus trichloride (0.275 g, 2.0 mmol) was added. The reaction mixture was stirred for 1 h at 60° C. and then concentrated in vacuo. The residue was purified on a silica gel column using chloroform/methanol/triethylamine, (90:10:1), as the eluent followed by further purification by washing with diethyl ether (3 mL) to give 0.050 g (24% yield) of the title compound as the base. The base (0.050 g, 0.12 mmol) was dissolved in chloroform/methanol, (1:1), and treated with HCl in diethyl ether (1 M) at 0° C. The resulting yellow crystals were collected by filtration and washed with diethyl ether to obtain 0.029 g (50% yield) of the title compound: 1H NMR (DMSO-d6, 400 MHz) δ 11.48 (br s, 1H), 10.74 (br s, 1H), 8.54 (br s, 1H), 8.27 (s, 1H), 8.11 (d, J=8.0 Hz, 1H), 8.03 (s, 1H), 7.87 (d, J=9.2 Hz, 1H), 7.59 (d, J=8.4 Hz, 1H), 6.98 (d, J=8.4 Hz, 1H), 4.29 (br s, 1H), 4.00 (d, J=11.2 Hz, 2H), 3.87 (d, J=11.2 Hz, 1H), 3.83 (d, J=12.4 Hz, 1H), 3.50 (br s, 4H), 3.38 (d, J=12.4 Hz, 2H), 3.32 (s, 3H), 3.13 (m, 2H); MS (EI) m/z 411 (M++1).

Workup

  1. customThe resulting reaction mixture
  2. stirringstirred for 1 h at 120° C.
  3. concentrationconcentrated in vacuo
  4. customThe remaining N,N-dimethylformamide was removed by co-evaporation with toluene (1×)
  5. customThe residue was purified on a silica gel column
  6. dissolutionThe material was dissolved in chloroform (4 mL)
  7. stirringThe reaction mixture was stirred for 1 h at 60° C.
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified on a silica gel column
  10. customfollowed by further purification
  11. washby washing with diethyl ether (3 mL)

Sources & evidence

ORD record
ord-788fc69ad7ac4dd89cabbe7894e7d0d5
Source dataset
uspto-grants-2010_03
Patent number
US07683067B2

Reaction notes

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