3,4-Dichloroaniline → N-(3,4-dichlorophenyl)-6-fluoropyrido[3,4-d]pyrimidin-4-amine

HRID 511798ノート

反応式

HRID 511798 の反応式
[F:1][C:2]1[N:12]=[CH:11][C:5]2[NH:6][C:7](=O)[N:8]=[CH:9][C:4]=2[CH:3]=1.S(Cl)(Cl)=O.[Cl:17][C:18]1[CH:19]=[C:20]([CH:22]=[CH:23][C:24]=1[Cl:25])[NH2:21]>CN(C=O)C.CC(N(C)C)=O>[Cl:17][C:18]1[CH:19]=[C:20]([NH:21][C:9]2[C:4]3[CH:3]=[C:2]([F:1])[N:12]=[CH:11][C:5]=3[N:6]=[CH:7][N:8]=2)[CH:22]=[CH:23][C:24]=1[Cl:25]

参加物

6

反応物 3

HCID 72573,4-DichloroanilineHCID 24386Thionyl ChlorideHCID 668235116-Fluoropyrido[3,4-d]pyrimidinone

生成物 1

HCID 68158723N-(3,4-dichlorophenyl)-6-fluoropyrido[3,4-d]pyrimidin-4-amine収率 100%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide触媒HCID 31374Dimethylacetamide溶媒

実験手順

A heterogeneous mixture of 6-fluoropyrido[3,4-d]pyrimidin-4(3H)-one (200) (1.50 g, 9.09 mmol), thionyl chloride (20 ml) and a catalytic amount of DMF (2 drops) was stirred under reflux for 1.5 h to give a homogeneous mixture. It was evaporated under reduced pressure at 50° C. (bath temperature) to give a light brown solid. To this solid was added a solution of 3,4-dichloroaniline (1.62 g, 10.0 mmol) in dry DMA (15 mL). The residue of 3,4-dichloroaniline was washed down with more DMA (2×2 ml). The reaction mixture was stirred at room temperature for 20 h. It was poured into water (200 mL). The pH was adjusted to ca. 8 using an aqueous solution of Na2CO3 at room temperature. Petroleum ether (300 mL) was added and stirred at room temperature for 30 min. The petroleum ether layer was decanted. It was repeated once more with petroleum ether. The solid was collected by filtration and washed with water (5×25 mL). It was dried in vacuum over silica gel/KOH overnight to give N-(3,4-dichlorophenyl)-6-fluoropyrido[3,4-d]pyrimidin-4-amine (204) (2.81 g, 100%) as a yellow/orange solid, mp 262-264° C.; 1H NMR δ [(CD3)2SO] 10.17 (s, 1H), 8.99 (s, 1H), 8.79 (s, 1H), 8.35 (d, J=2.5 Hz, 1H), 8.26 (poorly resolved d, J=0.7 Hz, 1H), 7.92 (dd, J=8.8, 2.5 Hz, 1H), 7.69 (d, J=8.8 Hz, 1H). Anal. Calcd for C13H7Cl2FN4: C, 50.51; H, 2.28; N, 18.12. Found C, 50.50; H, 2.27; N, 18.42.

後処理

  1. temperatureunder reflux for 1.5 h
  2. customto give a homogeneous mixture
  3. customIt was evaporated under reduced pressure at 50° C. (bath temperature)
  4. customto give a light brown solid
  5. washThe residue of 3,4-dichloroaniline was washed down with more DMA (2×2 ml)
  6. additionIt was poured into water (200 mL)
  7. customat room temperature
  8. additionPetroleum ether (300 mL) was added
  9. stirringstirred at room temperature for 30 min
  10. customThe petroleum ether layer was decanted
  11. filtrationThe solid was collected by filtration
  12. washwashed with water (5×25 mL)
  13. customIt was dried in vacuum over silica gel/KOH overnight

出典と根拠

ORDレコード
ord-d451332d24354c03822d6a556412adbd
出典データセット
uspto-grants-2015_08
特許番号
US09101632B2

反応ノート

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