Bromine → 6-(5-amino-[1,2,4]thiadiazol-3-ylthiomethyl)-3-tert-butoxycarbonyl-7-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepine

HRID 1670570ノート

反応式

HRID 1670570 の反応式
Cl.[C:2]([O:6][C:7]([N:9]1[CH2:15][CH2:14][C:13]2[C:16]([CH2:21][S:22][C:23](=[NH:25])[NH2:24])=[C:17]([Cl:20])[CH:18]=[CH:19][C:12]=2[CH2:11][CH2:10]1)=[O:8])([CH3:5])([CH3:4])[CH3:3].C[O-].[Na+].[C:29]([S-:31])#[N:30].[K+].BrBr>CO>[NH2:30][C:29]1[S:31][N:24]=[C:23]([S:22][CH2:21][C:16]2[C:13]3[CH2:14][CH2:15][N:9]([C:7]([O:6][C:2]([CH3:5])([CH3:3])[CH3:4])=[O:8])[CH2:10][CH2:11][C:12]=3[CH:19]=[CH:18][C:17]=2[Cl:20])[N:25]=1

参加物

6

反応物 4

HCID 24408BromineHCID 516872Potassium thiocyanateHCID 10942334Sodium MethoxideHCID 673354473-tert-Butoxycarbonyl-6-carbamimidoylthiomethyl-7-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepine hydrochloride

生成物 1

HCID 673359726-(5-amino-[1,2,4]thiadiazol-3-ylthiomethyl)-3-tert-butoxycarbonyl-7-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepine収率 43%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒2 回

反応条件

温度
0 °C

実験手順

To a solution of 3-tert-butoxycarbonyl-6-carbamimidoylthiomethyl-7-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepine hydrochloride (0.510 g, 1.256 mmol) in methanol (12.5 mL) at room temperature add solid sodium methoxide (0.14 g, 2.5 mmol) and then KSCN (0.12 g, 1.3 mmol). After cooling the reaction mixture to 0° C., add a solution of bromine (0.20 g, 1.3 mmol) in methanol (4 mL) dropwise. Stir the reaction mixture at room temperature overnight. Concentrate the reaction mixture in vacuo and partition the residue between DCM (100 mL) and water (50 mL). Extract the aqueous phase with DCM (50 mL). Dry the combined organic extracts over Na2SO4, filter and concentrate in vacuo. Dissolve the residue in DCM/methanol, add silica gel (5 g) and concentrate to a powder. Load the powder on to a dry column attached to a RediSep® column (40 g) and purify the crude mixture by preparative liquid chromatography (100:0 to 95:5 DCM/2M ammonia in methanol over 33 min; 95:5 to 80:20 DCM/2M ammonia in methanol over 33 min; 35 mL/min) to afford 6-(5-amino-[1,2,4]thiadiazol-3-ylthiomethyl)-3-tert-butoxycarbonyl-7-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.229 g, 43%). MS (ES+) m/z: 427.2 (M+H)+.

後処理

  1. concentrationConcentrate the reaction mixture in vacuo
  2. custompartition the residue between DCM (100 mL) and water (50 mL)
  3. extractionExtract the aqueous phase with DCM (50 mL)
  4. dry with materialDry the combined organic extracts over Na2SO4
  5. filtrationfilter
  6. concentrationconcentrate in vacuo
  7. dissolutionDissolve the residue in DCM/methanol
  8. additionadd silica gel (5 g)
  9. concentrationconcentrate to a powder
  10. custompurify the crude mixture by preparative liquid chromatography (100:0 to 95:5 DCM/2M ammonia in methanol over 33 min; 95:5 to 80:20 DCM/2M ammonia in methanol over 33 min; 35 mL/min)

出典と根拠

ORDレコード
ord-32572d1cd6f04582b00b2cb8acbc2c23
出典データセット
uspto-grants-2011_08
特許番号
US07994163B2

反応ノート

読み込み中…