2-Chloronicotinonitrile → 2-(1-Methyl-1H-indazol-5-yloxy)-nicotinonitrile

HRID 2112132Notes

Reaction equation

[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][C:7]([OH:11])=[CH:8][CH:9]=2)[CH:4]=[N:3]1.Cl[C:13]1[N:20]=[CH:19][CH:18]=[CH:17][C:14]=1[C:15]#[N:16]>CS(C)=O.O>[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][C:7]([O:11][C:13]3[N:20]=[CH:19][CH:18]=[CH:17][C:14]=3[C:15]#[N:16])=[CH:8][CH:9]=2)[CH:4]=[N:3]1

Participants

Conditions

Temperature: 110 °C

Procedure

1-Methyl-1H-indazol-5-ol (1n) (synthesized as described in Example 94) (0.10 g, 0.68 mmol) and 2-chloro-nicotinonitrile (2n) (0.11 g, 0.81 mmol) were suspended in DMSO (2 mL). The reaction mixture was heated to 110° C. for 18 hours. The reaction mixture was diluted with water and extracted into EtOAc. The combined organics were dried, Na2SO4 and concentrated under reduced pressure to afford the crude product. Purification by flash column chromatography (20-100% EtOAc/Hexanes) furnished the desired product (3n), (0.152 g, 90% yield). 1H NMR (400 mHz, CD3OD) δ 8.27-8.25 (m, 1H), 8.23-8.20 (m, 1H), 8.01 (s, 1H), 7.62 (d, J=8.6 Hz, 1H), 7.57 (d, J=2.3 Hz, 1H), 7.28-7.26 (m, 1H), 7.23-7.20 (m, 1H), 4.10 (s, 3H); MS (ESI+) m/z 251 (M+H) detected.

Workup

extractionextracted into EtOAc
customThe combined organics were dried
concentrationNa2SO4 and concentrated under reduced pressure
customto afford the crude product
customPurification by flash column chromatography (20-100% EtOAc/Hexanes)

Sources & evidence

ORD record: ord-e9e952b5731b4750b48e121cc4e26ea7
Source dataset: uspto-grants-2009_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07521447B2

Reaction notes

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