Trifluoroacetic acid → N-(2-cyclohexylethyl)-4-[({[(1-methyl-1H-tetrazol-5-yl)(phenyl)methylene]amino}oxy)methyl]-1,3-thiazol-2-amine

HRID 1258575Notes

Reaction equation

HRID 1258575 reaction equation
[CH3:1][N:2]1[C:6]([C:7](=[N:14][O:15][CH2:16][C:17]2[N:18]=[C:19]([NH:22][C:23](=O)OC(C)(C)C)[S:20][CH:21]=2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[N:5][N:4]=[N:3]1.[H-].[Na+].BrC[CH2:34][CH:35]1[CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]1.C(O)(C(F)(F)F)=O.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.C(Cl)Cl>[CH:35]1([CH2:34][CH2:23][NH:22][C:19]2[S:20][CH:21]=[C:17]([CH2:16][O:15][N:14]=[C:7]([C:6]3[N:2]([CH3:1])[N:3]=[N:4][N:5]=3)[C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=3)[N:18]=2)[CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]1

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 10340Sodium CarbonateHCID 15440(2-Bromoethyl)cyclohexaneHCID 24758Sodium hydrideHCID 86653132tert-butyl {4-[({[(1-methyl-1H-tetrazol-5-yl)(phenyl)methylene]amino}oxy)methyl]-1,3-thiazol-2-yl}carbamate

Product 1

HCID 86653131N-(2-cyclohexylethyl)-4-[({[(1-methyl-1H-tetrazol-5-yl)(phenyl)methylene]amino}oxy)methyl]-1,3-thiazol-2-amineYield 76%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

A stirred solution of tert-butyl {4-[({[(1-methyl-1H-tetrazol-5-yl)(phenyl)methylene]amino}oxy)methyl]-1,3-thiazol-2-yl}carbamate (0.185 g, 0.445 mmol, 1 eq.) in 3 ml of dry DMF was treated with NaH (60% dispn in mineral oil, 0.019 g, 0.49 mmol, 1.1 eq.) added in one portion. After 20 mins (2-bromoethyl)cyclohexane (0.096 g, 0.49 mmol, 1.1 eq.) was added and the reaction was stirred for 1 hr. Then TFA (1.48 g, 12.98 mmol, 30 eq.) was added carefully and the reaction was heated to 60° C. for 12 h. After cooling, sat. aqueous Na2CO3 was added followed by DCM. The layers were separated and the aqueous layer was extracted with DCM. The organics were combined, washed with sat. aqueous Na2CO3, dried over MgSO4 and concentrated. The crude was purified by chromatography on silica gel to give N-(2-cyclohexylethyl)-4-[({[(1-methyl-1H-tetrazol-5-yl)(phenyl)methylene]amino}oxy)methyl]-1,3-thiazol-2-amine (0.144 g, 76% yield) as a clear viscous oil.

Workup

  1. additionadded in one portion
  2. temperatureAfter cooling
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with DCM
  5. washwashed with sat. aqueous Na2CO3
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. customThe crude was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-253a7370ac834007999618c7ab5391a4
Source dataset
uspto-grants-2013_06
Patent number
US08466176B2

Reaction notes

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