Triethylamine → Tert-butyl 4-((2-(5-bromo-3-phenoxypyridin-2-ylamino)thiazol-4-yl)methyl)piperidine-1-carboxylate

HRID 1806186Notes

Reaction equation

HRID 1806186 reaction equation
Br[CH2:2][C:3](=O)[CH2:4][CH:5]1[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:7][CH2:6]1.[Br:19][C:20]1[CH:21]=[C:22]([O:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[C:23]([NH:26][C:27]([NH2:29])=[S:28])=[N:24][CH:25]=1.C(N(CC)CC)C>C(O)C>[Br:19][C:20]1[CH:21]=[C:22]([O:30][C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)[C:23]([NH:26][C:27]2[S:28][CH:2]=[C:3]([CH2:4][CH:5]3[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:7][CH2:6]3)[N:29]=2)=[N:24][CH:25]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 22243583Tert-butyl 4-(3-bromo-2-oxopropyl)piperidine-1-carboxylateHCID 866314811-(5-Bromo-3-phenoxypyridin-2-yl)thiourea

Product 1

HCID 57742615Tert-butyl 4-((2-(5-bromo-3-phenoxypyridin-2-ylamino)thiazol-4-yl)methyl)piperidine-1-carboxylateYield 92%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Heated a mixture tert-butyl 4-(3-bromo-2-oxopropyl)piperidine-1-carboxylate (1.38 g, 4.32 mmol), 1-(5-bromo-3-phenoxypyridin-2-yl)thiourea (1.0 g, 3.08 mmol), triethylamine (0.731 mL, 5.24 mmol), and ethanol (50 mL) at reflux overnight. Cooled to ambient temperature and partitioned between into water and ethyl acetate. Washed the organic layer with water, brine, dried and concentrated. Purified by MPLC (Biotage) eluting with 3:1 hexane:ethyl acetate to afford the title compound (1.54 g, 92%) as a white powder: 1H NMR (CDCl3) δ 8.66 (s, 1H), 8.13 (s, 1H), 7.43 (t, 2H), 7.25 (t, 1H), 7.12 (s, 1H), 7.06 (d, 2H), 6.45 (s, 1H), 4.08 (m, 2H), 2.67 (m, 2H), 2.56 (d, 2H), 1.85 (m, 1H), 1.66 (m, 2H), 1.44 (s, 9H), 1.15 (m, 2H).

Workup

  1. temperatureat reflux overnight
  2. custompartitioned between into water and ethyl acetate
  3. washWashed the organic layer with water, brine
  4. customdried
  5. concentrationconcentrated
  6. customPurified by MPLC (Biotage)
  7. washeluting with 3:1 hexane

Sources & evidence

ORD record
ord-ec7b7e3b6b0f460ea9bf008baeb6e0e7
Source dataset
uspto-grants-2013_01
Patent number
US08354540B2

Reaction notes

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