Triethylamine → HCID 86658428, compound

HRID 1185403Notes

Reaction equation

HRID 1185403 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[S:10][C:11]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[C:12]([C:14](=[O:29])[NH:15][C:16]2[CH:17]=[N:18][N:19]([CH3:28])[C:20]=2[CH:21]2[CH2:26][CH2:25][CH:24](O)[CH2:23][CH2:22]2)[N:13]=1.C(N(CC)CC)C.CS(Cl)(=O)=O.[N-:50]=[N+:51]=[N-:52].[Na+]>C(Cl)Cl.C1COCC1.C(OCC)(=O)C>[N:50]([CH:24]1[CH2:23][CH2:22][CH:21]([C:20]2[N:19]([CH3:28])[N:18]=[CH:17][C:16]=2[NH:15][C:14]([C:12]2[N:13]=[C:9]([C:3]3[C:4]([F:8])=[CH:5][CH:6]=[CH:7][C:2]=3[F:1])[S:10][C:11]=2[NH:30][C:31](=[O:37])[O:32][C:33]([CH3:34])([CH3:36])[CH3:35])=[O:29])[CH2:26][CH2:25]1)=[N+:51]=[N-:52]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 33557Sodium AzideHCID 67439041HCID 67439041, compound

Product 1

HCID 86658428HCID 86658428, compoundYield 30%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

tert-Butyl 2-(2,6-difluorophenyl)-4-(5-(4-hydroxycyclohexyl)-1-methyl-1H-pyrazol-4-ylcarbamoyl)thiazol-5-ylcarbamate (58 mg, 0.11 mmol) was dissolved in methylene chloride (3 mL) and THF (1.5 mL). Triethylamine (33 mg, 0.33 mmol) and methanesulfonyl chloride (19 mg, 0.16 mmol) were added and the mixture was stirred at room temperature for 2.5 h. The reaction was diluted with ethyl acetate (50 mL), washed with sat. sodium bicarbonate and brine and concentrated in vacuo (65 mg). The residue was dissolved in NMP (3.0 mL) and sodium azide (21.4 mg, 0.33 mmol) was added. The mixture was stirred at 85° C. overnight. After cooling to room temperature, the reaction was diluted with ethyl acetate, washed with water and brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified via flash chromatography, eluted with 0 to 100% ethyl acetate in heptane to give tert-butyl 4-(5-(4-azidocyclohexyl)-1-methyl-1H-pyrazol-4-ylcarbamoyl)-2-(2,6-difluorophenyl)thiazol-5-ylcarbamate (18 mg, 30%).

Workup

  1. washwashed with sat. sodium bicarbonate and brine
  2. concentrationconcentrated in vacuo (65 mg)
  3. dissolutionThe residue was dissolved in NMP (3.0 mL)
  4. stirringThe mixture was stirred at 85° C. overnight
  5. temperatureAfter cooling to room temperature
  6. washwashed with water and brine
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified via flash chromatography
  10. washeluted with 0 to 100% ethyl acetate in heptane

Sources & evidence

ORD record
ord-e09787e9067b4703a704d1340c2e3230
Source dataset
uspto-grants-2014_03
Patent number
US08669361B2

Reaction notes

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