Trifluoroacetic acid → HCID 58456313, compound

HRID 410523Notes

Reaction equation

HRID 410523 reaction equation
[Si]([O:8][C:9]1([C:13]2[S:14][C:15]([C:18]3[CH:19]=[C:20]([N:33]([C:41]4[N:46]=[C:45]([C:47]([F:50])([F:49])[F:48])[CH:44]=[CH:43][N:42]=4)C(=O)OC(C)(C)C)[CH:21]=[C:22]([NH:24][C:25](=[O:32])[NH:26][CH:27]4[CH2:31][CH2:30][CH2:29][CH2:28]4)[CH:23]=3)=[CH:16][N:17]=2)[CH2:12][CH2:11][CH2:10]1)(C(C)(C)C)(C)C.C(O)(C(F)(F)F)=O.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>ClCCl>[CH:27]1([NH:26][C:25]([NH:24][C:22]2[CH:21]=[C:20]([NH:33][C:41]3[N:46]=[C:45]([C:47]([F:48])([F:49])[F:50])[CH:44]=[CH:43][N:42]=3)[CH:19]=[C:18]([C:15]3[S:14][C:13]([C:9]4([OH:8])[CH2:10][CH2:11][CH2:12]4)=[N:17][CH:16]=3)[CH:23]=2)=[O:32])[CH2:28][CH2:29][CH2:30][CH2:31]1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 2724141Tetrabutylammonium FluorideHCID 67430919HCID 67430919, compound

Product 1

HCID 58456313HCID 58456313, compoundYield 28%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of the product of Step 3 (56 mg, 0.076 mmol) in dichloromethane (1 mL) was added TFA (1 mL) and the mixture was stirred for 60 minutes at room temperature. The mixture was concentrated in vacuo, then the residue was diluted with ethyl acetate (30 mL) and washed with sat. NaHCO3(aq) (30 mL) and brine (30 mL). The organic extracts were dried (Na2SO4) and concentrated in vacuo. The residue was dissolved in THF (1 mL), TBAF (228 μL, 1.0 M; 0.228 mmol) was added, and the mixture was stirred overnight at room temperature. The mixture was concentrated in vacuo, and the residue purified by chromatography on silica gel (100:0 to 80:20, ethyl acetate: EtOH) provided 9 mg (0.017 mmol, 28%) of the desired 1-cyclopentyl-3-(3-[2-(1-hydroxycyclobutyl)-1,3-thiazol-5-yl]-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)urea as a white solid. MS APCI: [M+H]+ m/z 519.1. 1H NMR (400 MHz, d6-acetone): δ 9.22 (s, 1H); 8.81 (d, J=4.9 Hz, 1H); 8.00-7.90 (m, 3H); 7.78 (s, 1H); 7.66 (s, 1H); 7.23 (d, J=4.9 Hz, 1H); 5.90 (d, J=7.0 Hz, 1H); 5.49 (s, 1H); 4.17-4.08 (m, 1H); 2.79-2.59 (m, 2H); 2.49-2.37 (m, 2H); 2.06-1.88 (m, 4H); 1.82-1.48 (m, 4H); 1.51-1.42 (m, 2H). rhSYK activity=+++

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. additionthe residue was diluted with ethyl acetate (30 mL)
  3. washwashed with sat. NaHCO3(aq) (30 mL) and brine (30 mL)
  4. dry with materialThe organic extracts were dried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. dissolutionThe residue was dissolved in THF (1 mL)
  7. stirringthe mixture was stirred overnight at room temperature
  8. concentrationThe mixture was concentrated in vacuo
  9. customthe residue purified by chromatography on silica gel (100:0 to 80:20, ethyl acetate: EtOH)

Sources & evidence

ORD record
ord-586151d733c94512a41fe781c0cdb08e
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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