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

HRID 911936Notes

Reaction equation

HRID 911936 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-b6d03f027ddb40868168c42928b0acaf
Source dataset
uspto-grants-2011_09
Patent number
US08022223B2

Reaction notes

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