Sodium Carbonate → Rilpivirine

HRID 1847136ノート

反応式

HRID 1847136 の反応式
Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]2[CH:16]=[CH:15][C:12]([C:13]#[N:14])=[CH:11][CH:10]=2)[N:3]=1.Cl.[CH3:18][C:19]1[CH:24]=[C:23]([CH:25]=[CH:26][C:27]#[N:28])[CH:22]=[C:21]([CH3:29])[C:20]=1[NH2:30].C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C>[CH3:18][C:19]1[CH:24]=[C:23](/[CH:25]=[CH:26]/[C:27]#[N:28])[CH:22]=[C:21]([CH3:29])[C:20]=1[NH:30][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]2[CH:16]=[CH:15][C:12]([C:13]#[N:14])=[CH:11][CH:10]=2)[N:3]=1

参加物

5

反応物 3

HCID 10340Sodium CarbonateHCID 111955954-((4-Chloropyrimidin-2-yl)amino)benzonitrileHCID 68291231HCID 68291231、化合物

生成物 1

HCID 6451164Rilpivirine収率 69.2%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

反応条件

温度
87.5 °C

実験手順

4-[(4-chloro-2-pyrimidinyl)amino]benzonitrile (100 gms) and 2,6-dimethyl-4-(2-cyanoethenyl) phenylamine hydrochloride (90.65 gms) were mixed with acetonitrile (800 ml) in an inert atmosphere and heated at 85-90° C. till completion of the reaction, as monitored by HPLC. The reaction mixture was cooled to 40° C. and pH of the reaction mass was adjusted to ≈ pH 10 with 20% sodium carbonate solution. The reaction mass was filtered at 5 to 10° C. and dried to yield Rilpivirine (110 gms). Rilpivirine thus obtained was dissolved in acetone (3600 ml) and after optional charcoal treatment was concentrated to 500 ml and was filtered at 5-10° C., dried to give Rilpivirine (80 gms), which was then added to dimethyl sulfoxide (338 ml) and heated to 70-75° C. The mixture was cooled to 50 to 55° C. and mixed with hydrochloric acid (25 ml) with constant stirring. Water (1350 ml) was added to the mixture at 40 to 45° C., which was stirred and cooled further. The reaction mass was filtered at 25 to 30° C. and the wet cake was dried to give 90 gms of Rilpivirine hydrochloride (I) having Z isomer less than 0.1%.

後処理

  1. temperatureThe reaction mixture was cooled to 40° C.
  2. filtrationThe reaction mass was filtered at 5 to 10° C.
  3. customdried

出典と根拠

ORDレコード
ord-d65342b354fd487eb26de670dd5cf1ac
出典データセット
uspto-grants-2015_02
特許番号
US08952155B2

反応ノート

読み込み中…