Dichloromethane → 5-amino-1-(2-bromo-6-chlorophenyl)-1H-pyrazole-4-carbonitrile

HRID 655721ノート

反応式

HRID 655721 の反応式
Cl.[Br:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([Cl:9])[C:4]=1[NH:10][NH2:11].C(Cl)Cl.[OH-].[Na+].C(O[CH:20]=[C:21]([C:24]#[N:25])[C:22]#[N:23])C>CO>[NH2:25][C:24]1[N:10]([C:4]2[C:5]([Cl:9])=[CH:6][CH:7]=[CH:8][C:3]=2[Br:2])[N:11]=[CH:20][C:21]=1[C:22]#[N:23]

参加物

6

反応物 4

HCID 6344DichloromethaneHCID 14798Sodium HydroxideHCID 671522-(Ethoxymethylene)propanedinitrileHCID 57504666(2-Bromo-6-chlorophenyl)hydrazine hydrochloride

生成物 1

HCID 574386615-amino-1-(2-bromo-6-chlorophenyl)-1H-pyrazole-4-carbonitrile収率 85%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

実験手順

(2-Bromo-6-chlorophenyl)hydrazine hydrochloride (Intermediate AH2) (4.71 g, 18.26 mmol) was partitioned between DCM (300 mL) and 2M NaOH (20 mL). Allowed to Stir for 1 hour. The two phases were separated. The organic phase was reduced under vacuum to give the free base. This was dissolved in MeOH (60 mL), and stirred in a cooling bath at 0° C. (Ethoxymethylene)malononitrile (2.230 g, 18.26 mmol) added portionwise. The reaction mixture was then allowed to warm to ambient temperature and stirred for 1 hour. The mixture was then heated to reflux and stirred for 16 hours. Allowed to cool to ambient temperature. The reaction mixture was concentrated to give a solid, which was triturated under MeOH. A solid was filtered off. This was dried to afford the product (4.59 g, 85%). 1H NMR (400 MHz, DMSO) δ 6.79 (2H, s), 7.54-7.47 (1H, m), 7.70 (1H, dd), 7.79 (1H, s), 7.81 (1H, d). m/z (ES+) (M+H)+=299; HPLC tR=1.70 min.

後処理

  1. customThe two phases were separated
  2. customto give the free base
  3. additionadded portionwise
  4. stirringstirred for 1 hour
  5. temperatureThe mixture was then heated
  6. temperatureto reflux
  7. stirringstirred for 16 hours
  8. temperatureAllowed to cool to ambient temperature
  9. concentrationThe reaction mixture was concentrated
  10. customto give a solid, which
  11. customwas triturated under MeOH
  12. filtrationA solid was filtered off
  13. customThis was dried

出典と根拠

ORDレコード
ord-862d4ba7191e48448c43559b9a778530
出典データセット
uspto-grants-2011_12
特許番号
US08071608B2

反応ノート

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