Diisopropylethylamine → tert-Butyl 4-((2-(5-bromo-3-(4-fluorophenoxy)pyridin-2-ylamino)thiazol-4-yl)methyl)-3-oxopiperazine-1-carboxylate

HRID 1806177Notes

Reaction equation

HRID 1806177 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([O:12][C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)[C:5]([NH:8][C:9]([NH2:11])=[S:10])=[N:6][CH:7]=1.Cl[CH2:21][C:22](=O)[CH2:23][N:24]1[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26][C:25]1=[O:37].CCN(C(C)C)C(C)C>C(O)C.C(OCC)(=O)C>[Br:1][C:2]1[CH:3]=[C:4]([O:12][C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)[C:5]([NH:8][C:9]2[S:10][CH:21]=[C:22]([CH2:23][N:24]3[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:35])([CH3:34])[CH3:36])=[O:31])[CH2:26][C:25]3=[O:37])[N:11]=2)=[N:6][CH:7]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 866314851-(5-Bromo-3-(4-fluorophenoxy)pyridin-2-yl)thioureaHCID 86631533tert-Butyl 4-(3-chloro-2-oxopropyl)-3-oxopiperazine-1-carboxylate

Product 1

HCID 57742856tert-Butyl 4-((2-(5-bromo-3-(4-fluorophenoxy)pyridin-2-ylamino)thiazol-4-yl)methyl)-3-oxopiperazine-1-carboxylateYield 25.1%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

In a 20 mL scintillation vial equipped with magnetic stirrer 1-(5-bromo-3-(4-fluorophenoxy)pyridin-2-yl)thiourea (0.25 g, 0.73 mmol) was suspended in ethanol (5 ml) and tert-butyl 4-(3-chloro-2-oxopropyl)-3-oxopiperazine-1-carboxylate (0.32 g, 1.10 mmol) was added followed by DIEA (0.22 mL, 1.28 mmol). Resulting mixture was heated to 60° C. and agitated for 3 hours. Mixture was then diluted with ethyl acetate and washed with sodium bicarbonate solution, brine, dried and evaporated. Purified by column chromatography on silica gel, eluting with 50-100% ethyl acetate/hexane to give the title compound (0.106 g, 25.1% yield). 1H NMR (CDCl3) δ 1.41 (s, 9H), 2.79-3.42 (m, 6H), 6.55 (s, 2H), 7.03-7.12 (m, 4-H), 8.12 (s, 1H), 8.95 (bs, 1H).

Workup

  1. customResulting mixture
  2. washwashed with sodium bicarbonate solution, brine
  3. customdried
  4. customevaporated
  5. customPurified by column chromatography on silica gel
  6. washeluting with 50-100% ethyl acetate/hexane

Sources & evidence

ORD record
ord-ee3e34dd4bba4f04a6701c8acdbb64ae
Source dataset
uspto-grants-2013_01
Patent number
US08354540B2

Reaction notes

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