Hydrazine → 2-(6-(6-(4-Fluorophenyl)imidazo[2,1-b]oxazol-5-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)ethanol

HRID 1711793Notes

Reaction equation

F[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]2[N:15]([C:16]=1[C:17]1[CH:18]=[N:19][C:20]([NH:23][NH2:24])=[CH:21][CH:22]=1)[CH:14]=[CH:13][O:12]2.FC1C=CC(C2N=C3N(C=2)C=CO3)=CC=1.[CH2:40]1C(=O)N(I)[C:42](=[O:43])[CH2:41]1.FC1C=CC(B(O)O)=CN=1.NN.[Si](OCCC=O)(C(C)(C)C)(C)C.C(O)(=O)C.C(O)(=O)C.IC1C=CC=CC=1>CO>[F:8][C:6]1[CH:5]=[CH:4][C:3]([C:9]2[N:10]=[C:11]3[N:15]([C:16]=2[C:17]2[CH:22]=[CH:21][C:20]4[N:19]([C:40]([CH2:41][CH2:42][OH:43])=[N:24][N:23]=4)[CH:18]=2)[CH:14]=[CH:13][O:12]3)=[CH:2][CH:7]=1

Participants

Conditions

Temperature: 65 °C

Procedure

The 6-(2,4-difluorophenyl)-5-(6-hydrazinylpyridin-3-yl)imidazo[2,1-b]oxazole (0.20 g, 0.65 mmol; prepared using A from 6-(4-fluorophenyl)-imidazo[2,1-b]oxazole [prepared according to WO2004110990A2, Example 1, Steps 1-3] with NIS, C with 2-fluoropyridine-5-boronic acid [Asymchem], D with hydrazine) and 3-(tert-butyldimethylsilyloxy)propanal (0.12 g, 0.65 mmol; Toronto) were dissolved in MeOH (5.0 mL) and heated to about 65° C. for about 1 h. The MeOH was evaporated then DCM (5 mL) was added followed by iodobenzene diacetate (0.21 g, 0.65 mmol). The reaction was stirred for about 16 h and then evaporated. The resulting solid was dissolved in 1M TBAF in THF (5 mL). The reaction was allowed to stir for about 30 min. The THF was evaporated and the crude material was purified by reverse phase HPLC (Table 1, Method f). The fractions containing product were concentrated under reduced pressure and the resulting precipitate was filtered and dried under vacuum for about 16 h at about 60° C. to provide the title compound (0.033 g, 14%) as a white solid: LC/MS (Table 1, Method a) Rt=1.76 min; MS m/z: 364.1 (M+H)+.

Workup

customprepared
customThe MeOH was evaporated
additionDCM (5 mL) was added
customevaporated
dissolutionThe resulting solid was dissolved in 1M TBAF in THF (5 mL)
stirringto stir for about 30 min
customThe THF was evaporated
customthe crude material was purified by reverse phase HPLC (Table 1, Method f)
additionThe fractions containing product
concentrationwere concentrated under reduced pressure
filtrationthe resulting precipitate was filtered
customdried under vacuum for about 16 h at about 60° C.

Sources & evidence

ORD record: ord-6e0462027c774273961b3dfd0c73820d
Source dataset: uspto-grants-2010_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07790741B2

Reaction notes

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