Phosphorus oxychloride → 5-bromo-N-(4-(2-(5-methyl-1,3,4-oxadiazol-2-yl)ethyl)thiazol-2-yl)-3-phenoxypyridin-2-amine

HRID 335194Notes

Reaction equation

[C:1]([NH:4][NH:5][C:6](=O)[CH2:7][CH2:8][C:9]1[N:10]=[C:11]([NH:14][C:15]2[C:20]([O:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[CH:19][C:18]([Br:28])=[CH:17][N:16]=2)[S:12][CH:13]=1)(=[O:3])[CH3:2].O=P(Cl)(Cl)Cl>C(#N)C>[Br:28][C:18]1[CH:19]=[C:20]([O:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:15]([NH:14][C:11]2[S:12][CH:13]=[C:9]([CH2:8][CH2:7][C:6]3[O:3][C:1]([CH3:2])=[N:4][N:5]=3)[N:10]=2)=[N:16][CH:17]=1

Participants

Conditions

Temperature: 50 °C

Procedure

To a mixture of N′-acetyl-3-(2-(5-bromo-3-phenoxypyridin-2-ylamino)thiazol-4-yl)propanehydrazide (0.100 g, 0.210 mmol) in 5 mL acetonitrile was added POCl3 (0.0769 mL, 0.840 mmol) and the reaction was heated at 50° C. for 72 hours. The mixture was concentrated to dryness, diluted with water and extracted with CH2C2. The organic layer was dried over Na2SO4 and purified by preparative HPLC to give the title compound (0.029 g, 30.1% yield). 1H NMR (d6 DMSO) δ 2.50 (2, 3H), 3.00 (t, J=7.4 Hz, 2H), 3.17 (t, J=7.5 Hz, 2H), 6.76 (s, 1H), 7.11 (d, J=7.6 Hz, 2H), 7.21 (t, J=7.3 Hz, 1H), 7.40 (d, J=2.0 Hz, 1H), 7.44 (t, J=7.9 Hz, 2H), 8.22 (d, J=2.2 Hz, 1H), 10.99 (s, 1H).

Workup

concentrationThe mixture was concentrated to dryness
additiondiluted with water
extractionextracted with CH2C2
dry with materialThe organic layer was dried over Na2SO4
custompurified by preparative HPLC

Sources & evidence

ORD record: ord-9ad8caaa224a4911b4aeb65992537976
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08883828B2

Reaction notes

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