Sodium Hydroxide → [5-(8-Bromo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-2-yl)-1-isopropyl-1H-[1,2,4]triazol-3-yl]-carbamic acid benzyl ester

HRID 707833

反応式

HRID 707833 の反応式
[Br:1][C:2]1[CH:18]=[CH:17][C:5]2[C:6]3[N:7]=[C:8]([C:14](O)=O)[S:9][C:10]=3[CH2:11][CH2:12][O:13][C:4]=2[CH:3]=1.C(N(C(C)C)CC)(C)C.CN(C(ON1[N:44]=[N:43][C:38]2[CH:39]=CC=N[C:37]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH2:52]([O:59][C:60]([NH:62][C:63](=[NH:66])SC)=[O:61])[C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1.C(=O)(O)[O-].[Na+].Cl.C(NN)(C)C.[OH-].[Na+].[O-]Cl.[Na+]>C1COCC1>[CH2:52]([O:59][C:60](=[O:61])[NH:62][C:63]1[N:66]=[C:14]([C:8]2[S:9][C:10]3[CH2:11][CH2:12][O:13][C:4]4[CH:3]=[C:2]([Br:1])[CH:18]=[CH:17][C:5]=4[C:6]=3[N:7]=2)[N:43]([CH:38]([CH3:37])[CH3:39])[N:44]=1)[C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1

参加物

10

反応物 8

HCID 14798Sodium HydroxideHCID 81531Diisopropylethylamine2 回HCID 855731-Isopropylhydrazine hydrochlorideHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 23665760Sodium HypochloriteHCID 579001668-Bromo-4,5-dihydrobenzo[2,3]oxepino[4,5-d]thiazole-2-carboxylic acidHCID 140362141Benzyl [amino(methylsulfanyl)methylene]carbamate

生成物 1

HCID 58204121[5-(8-Bromo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-2-yl)-1-isopropyl-1H-[1,2,4]triazol-3-yl]-carbamic acid benzyl ester収率 57%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
95 °C

実験手順

To a suspension of 8-bromo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid (1.86 g, 5.70 mmol) in anhydrous THF (75 mL) was added diisopropylethylamine (2 mL, 11.4 mmol), HATU (2.39 g, 6.27 mmol) and 1-benzyloxycarbonyl-2-methyl-isothiourea (1.47 g, 6.56 mmol) at RT. After stirring for 24 hours an aqueous saturated sodium bicarbonate solution was added and the mixture extracted with 1:1 EtOAc/THF solution (×2). The organic layers were combined, washed with brine, dried (Na2SO4) and concentrated in vacuo. The resulting solid was added to DMF (50 mL) and treated with diisopropylethylamine (4 mL, 22.8 mmol) and isopropylhydrazine hydrochloride (941 mg, 8.55 mmol). The mixture was heated to 95° C. and scrubbed with 1N NaOH solution and NaOCl solution. After 2 hours the mixture was allowed to cool to RT, extracted with EtOAc and washed with water. The organic layer was dried (Na2SO4) and concentrated in vacuo. The resultant residue was purified by flash chromatography (SiO2, gradient 0-50% EtOAc in cyclohexane) to afford [5-(8-Bromo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-2-yl)-1-isopropyl-1H-[1,2,4]triazol-3-yl]-carbamic acid benzyl ester (1.75 g, 57%). LCMS: RT=5.11 min, [M+H]+=540/542

後処理

  1. additionwas added
  2. extractionthe mixture extracted with 1:1 EtOAc/THF solution (×2)
  3. washwashed with brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. additionThe resulting solid was added to DMF (50 mL)
  7. temperatureto cool to RT
  8. extractionextracted with EtOAc
  9. washwashed with water
  10. dry with materialThe organic layer was dried (Na2SO4)
  11. concentrationconcentrated in vacuo
  12. customThe resultant residue was purified by flash chromatography (SiO2, gradient 0-50% EtOAc in cyclohexane)

出典と根拠

ORDレコード
ord-6e0357c0239247ff868129bd225bbaa9
出典データセット
uspto-grants-2015_11
特許番号
US09175009B2

関連ノート

読み込み中…