Diisopropylethylamine → 3-(2,4-dimethoxy-phenyl)-5-((1aS,5aR)-1,1,2-trimethyl-1,1a,5,5a-tetrahydro-3-thia-cyclopropa[a]pentalen-4-yl)-[1,2,4]oxadiazole

HRID 1821133Notes

Reaction equation

HRID 1821133 reaction equation
[OH:1][NH:2][C:3](=[NH:14])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[CH:6][C:5]=1[O:12][CH3:13].[CH3:15][C:16]1([CH3:29])[C@@H:18]2[CH2:19][C:20]3[C:24]([C@H:17]12)=[C:23]([CH3:25])[S:22][C:21]=3[C:26](O)=O.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[CH3:13][O:12][C:5]1[CH:6]=[C:7]([O:10][CH3:11])[CH:8]=[CH:9][C:4]=1[C:3]1[N:14]=[C:26]([C:21]2[S:22][C:23]([CH3:25])=[C:24]3[C:20]=2[CH2:19][C@H:18]2[C:16]([CH3:29])([CH3:15])[C@H:17]23)[O:1][N:2]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 57892448(1aS,5aR)-1,1,2-trimethyl-1,1a,5,5a-tetrahydro-3-thia-cyclopropa[a]pentalene-4-carboxylic acidHCID 178491259HCID 178491259, compound

Product 1

HCID 578924493-(2,4-dimethoxy-phenyl)-5-((1aS,5aR)-1,1,2-trimethyl-1,1a,5,5a-tetrahydro-3-thia-cyclopropa[a]pentalen-4-yl)-[1,2,4]oxadiazoleYield 9.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of N-hydroxy-2,4-dimethoxy-benzamidine (98 mg, 0.50 mmol), (1aS,5aR)-1,1,2-trimethyl-1,1a,5,5a-tetrahydro-3-thia-cyclopropa[a]pentalene-4-carboxylic acid (111 mg, 0.50 mmol), TBTU (178 mg, 0.55 mmol) and DIPEA (646 mg, 5 mmol) in DMF (4 mL) is stirred at rt for 45 min, then at 110° C. for 1 h. The reaction mixture is directly subjected to prep. HPLC purification (Phenomenex Aqua 75×30 mm, gradient with acetonitrile/water containing 0.5% formic acid) to give 3-(2,4-dimethoxy-phenyl)-5-((1aS,5aR)-1,1,2-trimethyl-1,1a,5,5a-tetrahydro-3-thia-cyclopropa[a]pentalen-4-yl)-[1,2,4]oxadiazole (19 mg) as a colourless lyophilisate; LC-MS: tR=1.17 min, [M+1]+=383.13; 1H NMR (CDCl3): δ 7.89 (d, J=8.8 Hz, 1H), 6.46 (dd, J=2.3, 8.8 Hz, 1H), 6.43 (d, J=2.3 Hz, 1H), 3.83 (s, 3H), 3.74 (s, 3H), 2.96 (dd, J=5.9, 18.8 Hz, 1H), 2.80 (d, J=18.8 Hz, 1H), 2.29 (s, 3H), 1.88-1.78 (m, 2H), 1.02 (s, 3H), 0.63 (s, 3H).

Workup

  1. waitat 110° C. for 1 h
  2. customHPLC purification (Phenomenex Aqua 75×30 mm, gradient with acetonitrile/water containing 0.5% formic acid)

Sources & evidence

ORD record
ord-dcc6324111c54a42bf79d23a158c3e5d
Source dataset
uspto-grants-2009_10
Patent number
US07605269B2

Reaction notes

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