Triethylamine → Tert-butyl 4-(2-(3-(2-bromo-4-fluorophenoxy)-5-(3-methoxyphenylthio)pyridin-2-ylamino)thiazol-4-yl)piperidine-1-carboxylate

HRID 335239Notes

Reaction equation

HRID 335239 reaction equation
[Br:1][C:2]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:3]=1[O:4][C:5]1[C:6]([NH:20][C:21]([NH2:23])=[S:22])=[N:7][CH:8]=[C:9]([S:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH3:19])[CH:13]=2)[CH:10]=1.C(N(CC)CC)C.Br[CH2:37][C:38]([CH:40]1[CH2:45][CH2:44][N:43]([C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[CH2:42][CH2:41]1)=O>CCO>[Br:1][C:2]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:3]=1[O:4][C:5]1[C:6]([NH:20][C:21]2[S:22][CH:37]=[C:38]([CH:40]3[CH2:41][CH2:42][N:43]([C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[CH2:44][CH2:45]3)[N:23]=2)=[N:7][CH:8]=[C:9]([S:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH3:19])[CH:13]=2)[CH:10]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 18187487tert-Butyl 4-(2-Bromoacetyl)piperidine-1-carboxylateHCID 866315271-(3-(2-Bromo-4-fluorophenoxy)-5-(3-methoxyphenylthio)pyridin-2-yl)thiourea

Product 1

HCID 86631529Tert-butyl 4-(2-(3-(2-bromo-4-fluorophenoxy)-5-(3-methoxyphenylthio)pyridin-2-ylamino)thiazol-4-yl)piperidine-1-carboxylateYield 82%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
70 °C

Procedure

A 50 mL round-bottomed flask was charged with 1-(3-(2-bromo-4-fluorophenoxy)-5-(3-methoxyphenylthio)pyridin-2-yl)thiourea (1.5 g, 3.12 mmol), triethylamine (0.740 mL, 5.31 mmol), tert-butyl 4-(2-bromoacetyl)piperidine-1-carboxylate (1.15 g, 3.75 mmol), and EtOH (25 mL). The reaction was heated to 70° C. for 3 hours. The reaction was cooled to room temperature and partitioned between EtOAc and water. The organic layer was dried over sodium sulfate, filtered and concentrated. The residue was purified on silica gel (10% EtOAc in hexanes) to afford (1.76 g, 82.0% yield).

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. custompartitioned between EtOAc and water
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified on silica gel (10% EtOAc in hexanes)
  7. customto afford (1.76 g, 82.0% yield)

Sources & evidence

ORD record
ord-af9263030208436cb80ca3557aad37ea
Source dataset
uspto-grants-2014_11
Patent number
US08883828B2

Reaction notes

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