1-Hydroxybenzotriazole → (1S,6R)-tert-Butyl 8-(2-(3-methyl-1,2,4-oxadiazol-5-yl)benzoyl)-3,8-diazabicyclo[4.2.0]octane-3-carboxylate

HRID 2174983Notes

Reaction equation

HRID 2174983 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:15][CH2:14][CH:13]2[CH:10]([NH:11][CH2:12]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:16][C:17]1[N:21]=[C:20]([C:22]2[CH:30]=[CH:29][CH:28]=[CH:27][C:23]=2[C:24](O)=[O:25])[O:19][N:18]=1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1>C(Cl)Cl>[CH3:16][C:17]1[N:21]=[C:20]([C:22]2[CH:30]=[CH:29][CH:28]=[CH:27][C:23]=2[C:24]([N:11]2[C@H:10]3[C@H:13]([CH2:14][CH2:15][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9]3)[CH2:12]2)=[O:25])[O:19][N:18]=1

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 231463052-(3-Methyl-1,2,4-oxadiazol-5-yl)benzoic acidHCID 43810891Tert-butyl 3,8-diazabicyclo[4.2.0]octane-3-carboxylate

Product 1

HCID 131732983(1S,6R)-tert-Butyl 8-(2-(3-methyl-1,2,4-oxadiazol-5-yl)benzoyl)-3,8-diazabicyclo[4.2.0]octane-3-carboxylateYield 64.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 3,8-diaza-bicyclo[4.2.0]octane-3-carboxylic acid tert-butyl ester (550 mg, 2.59 mmol) in CH2Cl2 (9 mL) was added 2-(3-methyl-1,2,4-oxadiazol-5-yl)benzoic acid (545 mg, 2.59 mmol) followed by EDCl (745 mg, 3.89 mmol), HOBt (525 mg, 3.89 mmol) and TEA (0.72 mL, 5.18 mmol). The mixture was stirred for 14 h at room temperature and then washed (2×) with saturated aqueous NH4Cl solution. The organic layer was dried over Na2SO4, filtered and concentrated in vacuo. Chromatography (Hex to 100% EtOAc/Hex) afforded the desired product as a colorless foam (665 mg, 61%). MS (ESI): mass calculated for C21H26N4O4, 398.20, m/z found 399.0 [M+1]+. 1H NMR (500 MHz, CDCl3): 8.14-8.05 (m, 1H), 7.67-7.52 (m, 2H), 7.45-7.36 (m, 1H), 4.39-4.21 (m, 2H), 4.04-3.96 (m, 1H), 3.90-3.83 (m, 0H), 3.77-3.43 (m, 3H), 2.96-2.76 (m, 2H), 2.47 (s, 3H), 2.03-1.72 (m, 2H), 1.54-1.36 (m, 9H).

Workup

  1. washwashed (2×) with saturated aqueous NH4Cl solution
  2. dry with materialThe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-690436e25fe941a7a0fe784e9ca4cbd5
Source dataset
uspto-grants-2015_06
Patent number
US09062044B2

Reaction notes

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