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 1530565Notes

Reaction equation

HRID 1530565 reaction equation
[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]

Participants

6

Reactant 4

HCID 11776Triphenylphosphine2×HCID 5363146Diisopropyl azodicarboxylate2×HCID 58348207Tert-butyl 3-(1-hydroxyethyl)azetidine-1-carboxylate2×HCID 1360309202-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-8-ol

Product 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 esterYield 66%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

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

Workup

  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)

Sources & evidence

ORD record
ord-2c5b79c97ccd45feaa1ebf4add5c93ab
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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