Diisopropylethylamine → 5-{5-[4-(Ethyloxy)-3,5-difluorophenyl]-1,2,4-oxadiazol-3-yl}isoquinoline
Reaction equation
[CH2:1]([O:3][C:4]1[C:12]([F:13])=[CH:11][C:7]([C:8]([OH:10])=O)=[CH:6][C:5]=1[F:14])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.O[NH:49][C:50]([C:52]1[C:53]2[CH:54]=[CH:55][N:56]=[CH:57][C:58]=2[CH:59]=[CH:60][CH:61]=1)=[NH:51]>CN(C)C=O>[CH2:1]([O:3][C:4]1[C:5]([F:14])=[CH:6][C:7]([C:8]2[O:10][N:51]=[C:50]([C:52]3[CH:61]=[CH:60][CH:59]=[C:58]4[C:53]=3[CH:54]=[CH:55][N:56]=[CH:57]4)[N:49]=2)=[CH:11][C:12]=1[F:13])[CH3:2]Participants
6
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
A mixture of 4-(ethyloxy)-3,5-difluorobenzoic acid (JRD Fluorochemicals Ltd; 130 mg, 0.641 mmol), HATU (244 mg, 0.641 mmol), Hunig's base (0.3 mL, 1.718 mmol) in N,N-dimethylformamide (DMF) (1 ml) was stirred at room temperature for 1 hr before the addition of N-hydroxy-5-isoquinolinecarboximidamide (D1; 100 mg, 0.534 mmol) in N,N-dimethylformamide (DMF) (1 ml). The reaction mixture was stirred at room temperature for 2-3 hrs and then heated in a microwave at 140° C. for 1.5 hr. The reaction mixture was concentrated in vacuo and purified by preparative HPLC (Waters Atlantis column, eluting with solvents A/B (A: Water+0.1% Formic acid, B: MeCN+0.1% Formic acid)) to give the title compound (11 mg)
Workup
- temperatureheated in a microwave at 140° C. for 1.5 hr
- concentrationThe reaction mixture was concentrated in vacuo
- custompurified by preparative HPLC (Waters Atlantis column
- washeluting with solvents A/B (A: Water+0.1% Formic acid, B
Sources & evidence
- ORD record
- ord-86653cf6080a474fb54d01a192077af1
- Source dataset
- uspto-grants-2012_12
- Patent number
- US08329730B2
Reaction notes
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