Diisopropylethylamine → 1,1-Dimethylethyl 3-{5-[5-(3-cyano-4-fluorophenyl)-1,2,4-oxadiazol-3-yl]-1-isoquinolinyl}propanoate

HRID 2192506Notes

Reaction equation

[C:1]([C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:11]=1[F:12])[C:6]([OH:8])=O)#[N: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:47][C:48](=[NH:68])[C:49]1[CH:58]=[CH:57][CH:56]=[C:55]2[C:50]=1[CH:51]=[CH:52][N:53]=[C:54]2[CH2:59][CH2:60][C:61]([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:62]>CN(C=O)C>[C:1]([C:3]1[CH:4]=[C:5]([C:6]2[O:8][N:47]=[C:48]([C:49]3[CH:58]=[CH:57][CH:56]=[C:55]4[C:50]=3[CH:51]=[CH:52][N:53]=[C:54]4[CH2:59][CH2:60][C:61]([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:62])[N:68]=2)[CH:9]=[CH:10][C:11]=1[F:12])#[N:2]

Participants

Conditions

Temperature: 120 °C

Procedure

3-Cyano-4-fluorobenzoic acid (D31; 0.288 g, 1.744 mmol) was stirred at room temperature in 5 ml of DMF with HATU (0.723 g, 1.903 mmol) and DIPEA (0.831 ml, 4.76 mmol) for 10 mins. 1,1-Dimethylethyl 3-{5-[(hydroxyamino)(imino)methyl]-1-isoquinolinyl}propanoate (D36, 0.5 g, 1.585 mmol) and 5 ml of DMF were added, and the resulting mixture was stirred in a Biotage Initiator microwave at 120° C. for 30 mins. The solvent was removed under vacuum and the residue was purified by column chromatography on silica, eluting with 0-40% ethyl acetate in cyclohexane, to give the title compound as a white solid (67 mg).

Workup

customThe solvent was removed under vacuum
customthe residue was purified by column chromatography on silica
washeluting with 0-40% ethyl acetate in cyclohexane

Sources & evidence

ORD record: ord-30c918605c5a46208b692c3caa255f10
Source dataset: uspto-grants-2012_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08329730B2

Reaction notes

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