Tetrahydrofuran → HCID 58456407, compound

HRID 410610Notes

Reaction equation

HRID 410610 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([C:19]2[S:23][C:22]([CH2:24][CH2:25]C(OCC)=O)=[N:21][CH:20]=2)[CH:5]=[C:6]([NH:8][C:9]2[N:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][N:10]=2)[CH:7]=1.[CH3:31][Mg]Br.[CH2:34]1[CH2:38][O:37]CC1>>[CH3:31][C:38]([OH:37])([CH2:25][CH2:24][C:22]1[S:23][C:19]([C:4]2[CH:5]=[C:6]([NH:8][C:9]3[N:14]=[C:13]([C:15]([F:17])([F:18])[F:16])[CH:12]=[CH:11][N:10]=3)[CH:7]=[C:2]([CH3:1])[CH:3]=2)=[CH:20][N:21]=1)[CH3:34]

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 67262162HCID 67262162, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 58456407HCID 58456407, compoundYield 75%

Conditions

Temperature
-78 °C

Procedure

Ethyl 3-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]-propanoate (Example 79-1, 100 mg, 0.229 mmol) was taken up in THF (5 mL) and cooled to −78° C. Methylmagnesium bromide (3.0 M in Et2O, 305 μL, 0.916 mmol) was added, and the reaction was stirred at −78° C. for 90 min. It was then warmed to room temperature. After 1 h at room temperature, the reaction was quenched with saturated NH4Cl and extracted with ethyl acetate (2×). The combined organic layers were washed with brine, dried (MgSO4), and evaporated. Column chromatography on silica (20-100% ethyl acetate in hexanes) afforded 2-methyl-4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]butan-2-ol (73 mg, 75%) as a white foam. MS ESI: [M+H]+ m/z 423.1. 1H NMR (600 MHz, DMSO-d6) δ 10.22 (s, 1H), 8.81 (d, J=4.8, 1H), 7.93 (s, 1H), 7.89 (s, 1H), 7.42 (s, 1H), 7.25 (d, J=4.8, 1H), 7.11 (s, 1H), 4.36 (s, 1H), 3.05-2.92 (m, 2H), 2.28 (s, 3H), 1.87-1.73 (m, 2H) 1.11 (s, 6H). rhSYK activity=+++

Workup

  1. temperatureIt was then warmed to room temperature
  2. waitAfter 1 h at room temperature
  3. customthe reaction was quenched with saturated NH4Cl
  4. extractionextracted with ethyl acetate (2×)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried (MgSO4)
  7. customevaporated

Sources & evidence

ORD record
ord-f70fa334e9394f9dba32ed45ccfd51e4
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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