Ethyl 4-[(5-{3-methyl-5-[(4-methylpyrimidin-2-yl)amino]phenyl}-1,3-thiazol-2-yl)methylidene]cyclohexanecarboxylate → Ethyl 4-[(5-{3-methyl-5-[(4-methylpyrimidin-2-yl)amino]phenyl}-1,3-thiazol-2-yl)methyl]cyclohexanecarboxylate

HRID 928150Notes

Reaction equation

HRID 928150 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([C:16]2[S:20][C:19]([CH:21]=[C:22]3[CH2:27][CH2:26][CH:25]([C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH2:24][CH2:23]3)=[N:18][CH:17]=2)[CH:5]=[C:6]([NH:8][C:9]2[N:14]=[C:13]([CH3:15])[CH:12]=[CH:11][N:10]=2)[CH:7]=1>C(O)C.[Pd]>[CH3:1][C:2]1[CH:3]=[C:4]([C:16]2[S:20][C:19]([CH2:21][CH:22]3[CH2:27][CH2:26][CH:25]([C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH2:24][CH2:23]3)=[N:18][CH:17]=2)[CH:5]=[C:6]([NH:8][C:9]2[N:14]=[C:13]([CH3:15])[CH:12]=[CH:11][N:10]=2)[CH:7]=1

Participants

4

Reactant 1

HCID 86720200Ethyl 4-[(5-{3-methyl-5-[(4-methylpyrimidin-2-yl)amino]phenyl}-1,3-thiazol-2-yl)methylidene]cyclohexanecarboxylate

Product 1

HCID 70983893Ethyl 4-[(5-{3-methyl-5-[(4-methylpyrimidin-2-yl)amino]phenyl}-1,3-thiazol-2-yl)methyl]cyclohexanecarboxylate

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

Ethyl 4-[(5-{3-methyl-5-[(4-methylpyrimidin-2-yl)amino]phenyl}-1,3-thiazol-2-yl)methylidene]cyclohexanecarboxylate (175 mg, 0.390 mmol) was taken up in ethanol (5 mL), and palladium on carbon (10% loading, 104 mg, 0.098 mmol) was added. The reaction was purged with hydrogen gas (3×) and stirred under a hydrogen atmosphere (via balloon) overnight at room temperature. The mixture was then filtered through CELITE, concentrated under reduced pressure, and the residue purified by flash chromatography on silica gel (0-50% ethyl acetate in hexanes) to provide ethyl 4-[(5-{3-methyl-5-[(4-methylpyrimidin-2-yl)amino]phenyl}-1,3-thiazol-2-yl)methyl]cyclohexanecarboxylate (yellow gum) as a 3:1 mixture of diastereomers. MS ESI calc'd. for C25H31N4O2S [M+H]+ 451. found 451. 1H NMR (500 MHz, DMSO-d6) δ 9.58 (s, 1H), 8.34 (d, J=5.0, 1H), 7.96 (s, 1H), 7.92 (s, 1H), 7.51 (s, 1H), 7.03 (s, 1H), 6.74 (d, J=5.0 Hz, 1H), 4.06 (q, J=7.1 Hz, 2H), 2.88 (d, J=7.3 Hz, 2H), 2.36 (s, 3H), 2.29 (s, 3H), 1.93-1.83 (m, 4H), 1.62-1.45 (m, 4H), 1.24 (d, J=9.5 Hz, 2H), 1.18-1.14 (m, 3H). rhSyk activity=++

Workup

  1. customThe reaction was purged with hydrogen gas (3×)
  2. filtrationThe mixture was then filtered through CELITE
  3. concentrationconcentrated under reduced pressure
  4. customthe residue purified by flash chromatography on silica gel (0-50% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-d52b1f9b8a8641b7ad85dcde6a2f8e60
Source dataset
uspto-grants-2016_03
Patent number
US09290490B2

Reaction notes

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