Triphenylphosphine → 3-{1-[2-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-8-yloxy]ethyl}azetidine-1-carboxylic acid tert-butyl ester

HRID 1530565노트

반응식

HRID 1530565 반응식
[CH:1]([N:4]1[C:8]([C:9]2[N:18]=[C:17]3[N:11]([CH2:12][CH2:13][O:14][C:15]4[CH:22]=[C:21]([OH:23])[CH:20]=[CH:19][C:16]=43)[CH:10]=2)=[N:7][CH:6]=[N:5]1)([CH3:3])[CH3:2].[C:24]([O:28][C:29]([N:31]1[CH2:34][CH:33]([CH:35](O)[CH3:36])[CH2:32]1)=[O:30])([CH3:27])([CH3:26])[CH3:25].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>O1CCOCC1>[C:24]([O:28][C:29]([N:31]1[CH2:34][CH:33]([CH:35]([O:23][C:21]2[CH:20]=[CH:19][C:16]3[C:17]4[N:11]([CH2:12][CH2:13][O:14][C:15]=3[CH:22]=2)[CH:10]=[C:9]([C:8]2[N:4]([CH:1]([CH3:3])[CH3:2])[N:5]=[CH:6][N:7]=2)[N:18]=4)[CH3:36])[CH2:32]1)=[O:30])([CH3:27])([CH3:26])[CH3:25]

참가 물질

6

반응물 4

HCID 11776Triphenylphosphine2회HCID 5363146Diisopropyl azodicarboxylate2회HCID 58348207Tert-butyl 3-(1-hydroxyethyl)azetidine-1-carboxylate2회HCID 1360309202-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-8-ol

생성물 1

HCID 683128283-{1-[2-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-8-yloxy]ethyl}azetidine-1-carboxylic acid tert-butyl ester수율 66%

시약·촉매·용매 1

HCID 312751,4-Dioxane용매

실험 절차

To a suspension of 2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-8-ol (300 mg, 0.96 mmol), 3-(1-hydroxyethyl)azetidine-1-carboxylic acid tert-butyl ester (213 mg, 1.06 mmol) and PPh3 (379 mg, 1.46 mmol) in dioxane (5 mL) was added DIAD (285 μL, 1.46 mmol) and the resulting yellow solution stirred at RT for 2 h. Further 3-(1-hydroxyethyl)azetidine-1-carboxylic acid tert-butyl ester (105 mg, 0.53 mmol), PPh3 (190 mg, 0.73 mmol) and DIAD (143 μL, 0.73 mmol) were added and the resulting mixture stirred for 2 h. The reaction mixture was partitioned between EtOAc and 1M NaOH, the organic phase dried (MgSO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si-PCC, gradient 0-10% MeOH in EtOAc) affording 3-{1-[2-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-8-yloxy]ethyl}azetidine-1-carboxylic acid tert-butyl ester (312 mg, 66%). LCMS: RT 3.76 min [M+H]+ 495.2

후처리

  1. stirringthe resulting mixture stirred for 2 h
  2. customThe reaction mixture was partitioned between EtOAc and 1M NaOH
  3. dry with materialthe organic phase dried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customThe resulting residue was purified by column chromatography (Si-PCC, gradient 0-10% MeOH in EtOAc)

출처 및 근거

ORD 기록
ord-2c5b79c97ccd45feaa1ebf4add5c93ab
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09090628B2

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