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

HRID 1670567ノート

反応式

HRID 1670567 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C:12]2[C:15]([CH2:20][SH:21])=[C:16]([Cl:19])[CH:17]=[CH:18][C:11]=2[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[C:23]1[S:27][C:26]([NH:28][CH2:29][CH:30]2[CH2:32][CH2:31]2)=[N:25][CH:24]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C:12]2[C:15]([CH2:20][S:21][C:23]3[S:27][C:26]([NH:28][CH2:29][CH:30]4[CH2:32][CH2:31]4)=[N:25][CH:24]=3)=[C:16]([Cl:19])[CH:17]=[CH:18][C:11]=2[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

参加物

5

反応物 3

HCID 10796Cesium carbonateHCID 598222763-tert-Butoxycarbonyl-7-chloro-6-mercaptomethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepineHCID 59822318N-(5-bromothiazol-2-yl)-cyclopropylmethylamine

生成物 1

HCID 866237063-tert-butoxycarbonyl-7-chloro-6-[2-(cyclopropylmethyl-amino)-thiazol-5-ylthiomethyl]-2,3,4,5-tetrahydro-1H-benzo[d]azepine収率 44%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a solution of 3-tert-butoxycarbonyl-7-chloro-6-mercaptomethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.202 g, 0.617 mmol) and N-(5-bromothiazol-2-yl)-cyclopropylmethylamine (0.14 g, 0.62 mmol) in anhydrous DMF (6.2 mL) at room temperature add cesium carbonate (0.22 g, 0.68 mmol). Stir at room temperature overnight and partition the reaction mixture between saturated aqueous NaHCO3 (50 mL) and DCM (100 mL). Dry the organic extract over Na2SO4, filter and concentrate in vacuo. Dissolve the residue in DCM, load the solution on to an Analogix® column (40 g) and purify the crude intermediate by preparative liquid chromatography (100:0 to 75:25 hexane/EtOAc over 30 min; 75:25 to 50:50 hexane/EtOAc over 33 min; 35 mL/min) to afford 3-tert-butoxycarbonyl-7-chloro-6-[2-(cyclopropylmethyl-amino)-thiazol-5-ylthiomethyl]-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.129 g, 44%). MS (ES+) m/z: 480.2 (M+H)+.

後処理

  1. custompartition the reaction mixture between saturated aqueous NaHCO3 (50 mL) and DCM (100 mL)
  2. customDry the
  3. extractionorganic extract over Na2SO4
  4. filtrationfilter
  5. concentrationconcentrate in vacuo
  6. dissolutionDissolve the residue in DCM
  7. customload the solution on to an Analogix® column (40 g) and purify the crude intermediate by preparative liquid chromatography (100:0 to 75:25 hexane/EtOAc over 30 min; 75:25 to 50:50 hexane/EtOAc over 33 min; 35 mL/min)

出典と根拠

ORDレコード
ord-6e3cf61f8efa476d8c0144513a632a08
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…