Ammonium Chloride → 5-methyl-1-(5-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo-[3.1.0]hex-3-yl}pentyl)-2,4(1H,3H)-pyrimidinedione hydrochloride

HRID 12751ノート

反応式

HRID 12751 の反応式
[F:1][C:2]([F:16])([F:15])[C:3]1[CH:8]=[CH:7][C:6]([C@:9]23[CH2:14][C@H:13]2[CH2:12][NH:11][CH2:10]3)=[CH:5][CH:4]=1.[Cl:17][CH:18]([CH3:31])[CH2:19][CH2:20][CH2:21][N:22]1[CH:27]=[C:26]([CH3:28])[C:25](=[O:29])[NH:24][C:23]1=[O:30].[Cl-].[NH4+]>CN(C=O)C>[ClH:17].[CH3:28][C:26]1[C:25](=[O:29])[NH:24][C:23](=[O:30])[N:22]([CH2:21][CH2:20][CH2:19][CH2:18][CH2:31][N:11]2[CH2:12][C@H:13]3[C@:9]([C:6]4[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:15])[F:16])=[CH:8][CH:7]=4)([CH2:14]3)[CH2:10]2)[CH:27]=1

参加物

5

反応物 3

HCID 25517Ammonium ChlorideHCID 59337591(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexaneHCID 686935801-(4-chloropentyl)-5-methyl-2,4(1H,3H)-pyrimidinedione

生成物 1

HCID 686879535-methyl-1-(5-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo-[3.1.0]hex-3-yl}pentyl)-2,4(1H,3H)-pyrimidinedione hydrochloride収率 35.1%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
100 °C

実験手順

A mixture of (1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane (41 mg), 1-(4-chloropentyl)-5-methyl-2,4(1H,3H)-pyrimidinedione (Prep11, 50 mg) and TEA (50 μl) in DMF (0.5 mL) was heated at 100° C. overnight. Ammonium chloride was then added and the solution was extracted with dichloromethane. The organic phase was dried and concentrated in vacuo. The crude product was purified by a SCX cartridge followed by a preparative HPLC [column: ABZ plus 20×100 mm, 5 uM, mobile phase A: H2O+0.1% formic acid, mobile phase B: acetonitrile+0.1% formic acid, gradient: from 1 to 20% (B) in 10 min, flow rate: 20 mL/min, UV wavelength range: 210-350 nm, ionization: ES+, mass range: 100-900 amu (ES+)], to give 29 mg of the title compound which was further purified by flash chromatography eluting with DCM/MeOH/NH4OH from 99/1/0.1, to 98/2/0.1, to 97/3/0.1 to give the free base of the title compound (25 mg).

後処理

  1. extractionthe solution was extracted with dichloromethane
  2. customThe organic phase was dried
  3. concentrationconcentrated in vacuo
  4. customThe crude product was purified by a SCX cartridge
  5. customfollowed by a preparative HPLC [column: ABZ plus 20×100 mm, 5 uM, mobile phase A: H2O+0.1% formic acid, mobile phase B: acetonitrile+0.1% formic acid, gradient: from 1 to 20% (B) in 10 min, flow rate: 20 mL/min, UV wavelength range: 210-350 nm, ionization: ES+, mass range: 100-900 amu (ES+)]

出典と根拠

ORDレコード
ord-2c6f8300a25b4e1abc55717cd57e132b
出典データセット
uspto-grants-2010_06
特許番号
US07727988B2

反応ノート

読み込み中…