HCID 67431287, compound → HCID 67260166, compound

HRID 410656Notes

Reaction equation

HRID 410656 reaction equation
[OH:1][C:2]1([C:15]2[S:16][C:17]([C:20]3[CH:25]=[C:24]([CH3:26])[CH:23]=[C:22]([NH:27][C:28]4[N:33]=[C:32](/[CH:34]=[CH:35]/[CH2:36][O:37][CH3:38])[CH:31]=[CH:30][N:29]=4)[CH:21]=3)=[CH:18][N:19]=2)[CH2:7][CH2:6][CH:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1>CCO.[Pd]>[OH:1][C:2]1([C:15]2[S:16][C:17]([C:20]3[CH:25]=[C:24]([CH3:26])[CH:23]=[C:22]([NH:27][C:28]4[N:33]=[C:32]([CH2:34][CH2:35][CH2:36][O:37][CH3:38])[CH:31]=[CH:30][N:29]=4)[CH:21]=3)=[CH:18][N:19]=2)[CH2:3][CH2:4][CH:5]([C:8]([O:10][C:11]([CH3:13])([CH3:12])[CH3:14])=[O:9])[CH2:6][CH2:7]1

Participants

4

Reactant 1

HCID 67431287HCID 67431287, compound

Product 1

HCID 67260166HCID 67260166, compoundYield 28.4%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Conditions

Temperature
23 °C

Procedure

A solution of tert-butyl 4-hydroxy-4-{5-[3-({4-[(1E)-3-methoxyprop-1-en-1-yl]pyrimidin-2-yl}amino)-5-methylphenyl]-1,3-thiazol-2-yl}cyclohexanecarboxylate (100 mg, 0.19 mmol, 1.0 equiv) was dissolved in absolute EtOH (10 ml), deoxygenated, and treated with 10% Pd on carbon (50 mg, 0.47 mmol, 2.5 equiv). The mixture was deoxygenated further before being placed under hydrogen balloon and stirred for at 23° C. for 1 h. The reaction was 50% complete so it was maintained under H2 at 23° C. for another 1 h. The black mixture was filtered through a pad of Celite, which was then washed with EtOAc, dichloromethane, and MeOH. The filtrate was concentrated in vacuo, then purified by reverse-phase HPLC (acetonitrile/water gradient with 0.05% TFA present). The TFA salt was converted to the free base by partitioning between EtOAc (60 ml) and saturated aqueous NaHCO3 (70 ml). The organic layers were dried over MgSO4, filtered and concentrated to afford the title compound (29.1 mg, 27.5%) as a yellow-orange oil. MS ESI: [M+H]+ m/z 539.1. 1H NMR (500 MHz, CDCl3) δ 8.29 (d, J=3.4 Hz, 1H), 7.90 (m, 1H), 7.84 (s, 1H), 7.32 (s, 1H), 7.00 (s, 1H), 6.61 (m, 1H), 3.46-3.45 (m, 5H), 2.74-2.72 (m, 2H), 2.36 (s, 3H), 2.30 (m, 1H), 2.15-2.00 (m, 6H), 1.92-1.85 (m, 4H), 1.45 (s, 9H). rhSYK activity=++

Workup

  1. customdeoxygenated
  2. customThe mixture was deoxygenated further
  3. temperaturewas maintained under H2 at 23° C. for another 1 h
  4. filtrationThe black mixture was filtered through a pad of Celite, which
  5. washwas then washed with EtOAc, dichloromethane, and MeOH
  6. concentrationThe filtrate was concentrated in vacuo
  7. custompurified by reverse-phase HPLC (acetonitrile/water gradient with 0.05% TFA present)
  8. customby partitioning between EtOAc (60 ml) and saturated aqueous NaHCO3 (70 ml)
  9. dry with materialThe organic layers were dried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-042fccd502d04048839466504e99027b
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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