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 1849013

반응식

HRID 1849013 반응식
[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

참가 물질

10

반응물 8

HCID 14798Sodium HydroxideHCID 81531Diisopropylethylamine2회HCID 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

생성물 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 ester수율 57%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

반응 조건

온도
95 °C

실험 절차

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

후처리

  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)

출처 및 근거

ORD 기록
ord-e8fc60ffde3342dba98b347870e11740
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08952043B2

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