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

HRID 1806120Notes

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 CH2Cl2. 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 CH2Cl2
dry with materialThe organic layer was dried over Na2SO4
custompurified by preparative HPLC

Sources & evidence

ORD record: ord-a028caa357bd439cb5abece7a8eea196
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08354540B2

Reaction notes

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