Phosphorus trichloride → N-(7-(2-chlorophenyl)-2,6-naphthyridin-3-yl)cyclopropanecarboxamide

HRID 1502370Notes

Reaction equation

HRID 1502370 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N+:9]([O-])=[CH:10][C:11]2[C:16]([CH:17]=1)=[CH:15][N:14]=[C:13]([NH:18][C:19]([CH:21]1[CH2:23][CH2:22]1)=[O:20])[CH:12]=2.P(Cl)(Cl)Cl>ClCCl>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:17]=[C:16]2[C:11]([CH:12]=[C:13]([NH:18][C:19]([CH:21]3[CH2:22][CH2:23]3)=[O:20])[N:14]=[CH:15]2)=[CH:10][N:9]=1

Participants

4

Reactant 2

HCID 24387Phosphorus trichlorideHCID 679746713-(2-Chlorophenyl)-7-(cyclopropanecarboxamido)-2,6-naphthyridine 2-oxide

Product 1

HCID 68095280N-(7-(2-chlorophenyl)-2,6-naphthyridin-3-yl)cyclopropanecarboxamideYield 46.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a slurry of 3-(2-chlorophenyl)-7-(cyclopropanecarboxamido)-2,6-naphthyridine 2-oxide (170 mg, 0.5 mmol) in dichloromethane (2 mL) was added phosphorus trichloride (0.048 mL, 0.55 mmol) and the mixture was stirred at room temperature for 1 hour. The reaction mixture was then diluted with dichloromethane (50 mL) and washed with saturated sodium bicarbonate solution (30 mL). The organic layer was separated, dried over sodium sulfate, filtered, and evaporated in vacuo to afford a residue that was purified by flash chromatography (silica, 12 g, ISCO, 0-60% ethyl acetate in heptane) to afford the title compound as a white solid (75 mg, 46%). 1H NMR (400 MHz, DMSO) δ 11.17 (s, 1H), 9.46 (s, 1H), 9.35 (s, 1H), 8.66 (s, 1H), 8.23 (s, 1H), 7.76-7.67 (m, 1H), 7.63 (m, 1H), 7.55-7.43 (m, 2H), 2.14-2.06 (m, 1H), 0.88 (m, 4H). LCMS (Method D): RT=13.170 min, M+H+=324.0.

Workup

  1. washwashed with saturated sodium bicarbonate solution (30 mL)
  2. customThe organic layer was separated
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customto afford a residue that
  7. customwas purified by flash chromatography (silica, 12 g, ISCO, 0-60% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-bdb62a5597d84ee78b2b5dfd757c2d9a
Source dataset
uspto-grants-2015_12
Patent number
US09206175B2

Reaction notes

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