Diisopropylethylamine → 1-(4-(2-(5-Bromo-3-phenoxypyridin-2-ylamino)thiazol-4-yl)piperidin-1-yl)ethanone

HRID 1809556Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[C:4]([O:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:5]([NH:8][C:9]([NH2:11])=[S:10])=[N:6][CH:7]=1.[C:19]([N:22]1[CH2:27][CH2:26][CH:25]([C:28](=O)[CH2:29]Br)[CH2:24][CH2:23]1)(=[O:21])[CH3:20].CCN(C(C)C)C(C)C>C(O)C>[Br:1][C:2]1[CH:3]=[C:4]([O:12][C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:5]([NH:8][C:9]2[S:10][CH:29]=[C:28]([CH:25]3[CH2:26][CH2:27][N:22]([C:19](=[O:21])[CH3:20])[CH2:23][CH2:24]3)[N:11]=2)=[N:6][CH:7]=1

Participants

Conditions

Temperature: 60 °C

Procedure

1-(5-bromo-3-phenoxypyridin-2-yl)thiourea (Example 1, Step E; 30.0 g, 92.5 mmol) and 1-(1-acetylpiperidin-4-yl)-2-bromoethanone (Example 2, Step C, 32.1 g, 130 mmol) were suspended in ethanol (400 mL) and DIEA (48.3 mL, 278 mmol) was added. The resulting mixture was heated to 60° C. for 4 hours and then at ambient temperature overnight. The reaction was concentrated to dryness, dissolved in CH2Cl2 and washed with saturated aqueous sodium bicarbonate, water, dried over Na2SO4, filtered and concentrated. The resulting material was purified on silica eluting with 3% MeOH/EtOAc to give 1-(4-(2-(5-bromo-3-phenoxypyridin-2-ylamino)thiazol-4-yl)piperidin-1-yl)ethanone (41.6 g, 95.0% yield) as a tan solid.

Workup

customat ambient temperature
customovernight
concentrationThe reaction was concentrated to dryness
dissolutiondissolved in CH2Cl2
washwashed with saturated aqueous sodium bicarbonate, water
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated
customThe resulting material was purified on silica eluting with 3% MeOH/EtOAc

Sources & evidence

ORD record: ord-2a62af230fc1401796fc64038f9b279e
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08362037B2

Reaction notes

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