Urea → HCID 67430919, compound

HRID 410522Notes

Reaction equation

HRID 410522 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([N:25]([C:33]2[N:38]=[C:37]([C:39]([F:42])([F:41])[F:40])[CH:36]=[CH:35][N:34]=2)[C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29])[CH:5]=[C:6]([C:8]2[S:12][C:11]([C:13]3([O:17][Si:18]([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19])[CH2:16][CH2:15][CH2:14]3)=[N:10][CH:9]=2)[CH:7]=1.[N:43]([CH:46]1[CH2:50][CH2:49][CH2:48][CH2:47]1)=[C:44]=[O:45].NC(N)=O.[N-]=C=O>C1COCC1.C(OCC)(=O)C.CCN(CC)CC>[Si:18]([O:17][C:13]1([C:11]2[S:12][C:8]([C:6]3[CH:5]=[C:4]([N:25]([C:33]4[N:38]=[C:37]([C:39]([F:40])([F:41])[F:42])[CH:36]=[CH:35][N:34]=4)[C:26](=[O:32])[O:27][C:28]([CH3:30])([CH3:31])[CH3:29])[CH:3]=[C:2]([NH:1][C:44](=[O:45])[NH:43][CH:46]4[CH2:50][CH2:49][CH2:48][CH2:47]4)[CH:7]=3)=[CH:9][N:10]=2)[CH2:14][CH2:15][CH2:16]1)([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:19])[CH3:20]

Participants

8

Reactant 4

HCID 1176UreaHCID 105034IsocyanateHCID 643500Cyclopentyl IsocyanateHCID 67432108HCID 67432108, compound

Product 1

HCID 67430919HCID 67430919, compoundYield 86.7%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of the product of Step 2 (56 mg; 0.090 mmol) in THF (0.9 mL) was added triethylamine (38 μL; 0.27 mmol) followed by the isocyanatocyclopentane (31 μL; 0.27 mmol), then the mixture was stirred at room temperature overnight, at which point LC-UV analysis indicated ˜70% conversion to the desired urea. Additional Et3N and isocyanate (0.27 mmol each) were added, and the mixture was heated to 50° C. for 3 hours, at which point LC-UV indicated complete conversion. The mixture was diluted with ethyl acetate (30 mL) and washed with water (30 mL) and brine (30 mL). The organic extracts were dried (Na2SO4) and concentrated in vacuo. Purification by chromatography on silica gel (90:10 to 40:60, hexanes:ethyl acetate) provided 57 mg (0.078 mmol, 86%) of tert-butyl {3-[2-(1-{[tert-butyl(dimethyl)silyl]oxy}cyclobutyl)-1,3-thiazol-5-yl]-5-[(cyclopentylcarbamoyl)amino]phenyl}[4-(trifluoromethyl)pyrimidin-2-yl]carbamate as a white foam.

Workup

  1. temperaturethe mixture was heated to 50° C. for 3 hours, at which point LC-UV
  2. washwashed with water (30 mL) and brine (30 mL)
  3. dry with materialThe organic extracts were dried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customPurification by chromatography on silica gel (90:10 to 40:60, hexanes:ethyl acetate)

Sources & evidence

ORD record
ord-966ed15eda8245db877edf0dba7654cb
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

Loading…