Trifluoroacetic acid → HCID 178460037, compound

HRID 499081Notes

Reaction equation

HRID 499081 reaction equation
C(O[C:6]([N:8]1[CH2:16][C:10]2([O:13][CH2:12][C:11]2([CH3:15])[CH3:14])[CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O.C(N(C(C)C)CC)(C)C.ClC1[CH:39]=[C:38]([NH:40][C:41]2[NH:42][N:43]=[C:44]([CH3:46])[CH:45]=2)[N:37]=[C:36]([S:47][C:48]2[CH:53]=[CH:52][C:51]([NH:54][C:55](=[O:58])[CH2:56][CH3:57])=[CH:50][CH:49]=2)[N:35]=1>C(Cl)Cl.CCCCO.[Cl-].[Na+].O.C(OCC)(=O)C>[CH3:15][C:11]1([CH3:14])[C:10]2([CH2:9][N:8]([C:6]3[CH:39]=[C:38]([NH:40][C:41]4[NH:42][N:43]=[C:44]([CH3:46])[CH:45]=4)[N:37]=[C:36]([S:47][C:48]4[CH:53]=[CH:52][C:51]([NH:54][C:55](=[O:58])[CH2:56][CH3:57])=[CH:50][CH:49]=4)[N:35]=3)[CH2:16]2)[O:13][CH2:12]1

Participants

9

Reactant 4

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 59420847HCID 59420847, compoundHCID 178460036HCID 178460036, compound

Product 1

HCID 178460037HCID 178460037, compoundYield 21.7%

Reagents, catalysts & solvents 4

HCID 2631-ButanolSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of 3,3-Dimethyl-1-oxa-6-aza-spiro[3.3]heptane-6-carboxylic acid tert-butyl ester (60 mg, 0.27 mmol) in DCM (3 ml) at 0° C. was added trifluoroacetic acid and the reaction stirred at room temperature for 1 hr. The reaction was concentrated to give an oil which was used crude in the next step. The oily residue was dissolved in n-BuOH (3 ml) and diisopropylethylamine (171 mg, 1.35 mmol, 0.24 ml) and N-{4-[4-Chloro-6-(5-methyl-2H-pyrazol-3-ylamino)-pyrimidin-2-ylsulfanyl]-phenyl}-propionamide (93 mg, 0.24 mmol) was added. The mixture was heated to 100° C. and stirred for 18 hrs. The reaction was allowed to cool to room temperature and diluted with brine (20 ml) and ethyl acetate (20 ml). The organic layer was dried (Na2SO4) and concentrated to give an oil. The oil was purified by flash column chromatography eluting with 2.5% MeOH in ethyl acetate to give the title compound as a pale orange solid 25 mg, 20%. 1H NMR (d6-DMSO, 400 MHz) 1.08 (3H, m), 1.20 (6H, s), 1.98 (3H, s), 2.34 (2H, q), 3.78 (2H, d), 4.14-4.15 (4H, m), 5.35 (1H, s), 5.61 (1H, brs), 7.47 (2H, d), 7.70 (2H, d), 9.24 (1H, s), 10.07 (1H, s), 11.43 (1H, s). ES+ 480.

Workup

  1. concentrationThe reaction was concentrated
  2. customto give an oil which
  3. temperatureThe mixture was heated to 100° C.
  4. stirringstirred for 18 hrs
  5. temperatureto cool to room temperature
  6. dry with materialThe organic layer was dried (Na2SO4)
  7. concentrationconcentrated
  8. customto give an oil
  9. customThe oil was purified by flash column chromatography
  10. washeluting with 2.5% MeOH in ethyl acetate

Sources & evidence

ORD record
ord-eb3b3df3f7c2477bb9425e2cba18560f
Source dataset
uspto-grants-2010_08
Patent number
US07767672B2

Reaction notes

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