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

HRID 928149Notes

Reaction equation

HRID 928149 reaction equation
Br[C:2]1[S:6][C:5]([CH:7]=[C:8]2[CH2:13][CH2:12][CH:11]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH2:10][CH2:9]2)=[N:4][CH:3]=1.[CH3:19][C:20]1[CH:25]=[CH:24][N:23]=[C:22]([NH:26][C:27]2[CH:32]=[C:31](B3OC(C)(C)C(C)(C)O3)[CH:30]=[C:29]([CH3:42])[CH:28]=2)[N:21]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1>[CH3:42][C:29]1[CH:30]=[C:31]([C:2]2[S:6][C:5]([CH:7]=[C:8]3[CH2:13][CH2:12][CH:11]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH2:10][CH2:9]3)=[N:4][CH:3]=2)[CH:32]=[C:27]([NH:26][C:22]2[N:21]=[C:20]([CH3:19])[CH:25]=[CH:24][N:23]=2)[CH:28]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 584562194-methyl-N-[3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]pyrimidin-2-amineHCID 86720196Ethyl 4-[(5-bromo-1,3-thiazol-2-yl)methylidene]cyclohexanecarboxylate

Product 1

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

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

Ethyl 4-[(5-bromo-1,3-thiazol-2-yl)methylidene]cyclohexanecarboxylate (223 mg, 0.676 mmol), 4-methyl-N-[3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]pyrimidin-2-amine (220 mg, 0.676 mmol) and 1,1′-bis(diphenylphosphino)-ferrocenedichloro palladium(II) dichloromethane complex (49.5 mg, 0.068 mmol) were combined in a flask that was then sealed and flushed with nitrogen (2×). Dioxane (4 mL) and sodium carbonate (2 M in water, 1.015 mL, 2.029 mmol) were added, and the reaction was flushed again with nitrogen (2×). The mixture was heated to 80° C. for 1 hour and then cooled to room temperature, diluted with water and extracted with EtOAc (2×). The combined organic layers were washed with brine, dried over magnesium sulfate and concentrated under reduced pressure. Purification of the residue by chromatography on silica gel (5-60% EtOAc in hexanes) afforded ethyl 4-[(5-{3-methyl-5-[(4-methylpyrimidin-2-yl)amino]phenyl}-1,3-thiazol-2-yl)methylidene]cyclohexanecarboxylate as a yellow foam. MS ESI calc'd. for C25H29N4O2S [M+H]+ 449. found 449. 1H NMR (500 MHz, DMSO-d6) δ 9.59 (s, 1H), 8.34 (d, J=5.0, 1H), 8.05 (s, 1H), 8.02 (s, 1H), 7.51 (s, 1H), 7.07 (s, 1H), 6.74 (d, J=5.0 Hz, 1H), 6.46 (s, 1H), 4.06 (q, J=7.1 Hz, 2H), 3.55-3.47 (m, 1H), 3.31 (s, 2H), 2.66-2.57 (m, 1H), 2.44-2.24 (m, 7H), 2.04-1.97 (m, 2H), 1.61-1.46 (m, 2H), 1.17 (t, J=7.1 Hz, 3H).

Workup

  1. customthat was then sealed
  2. customflushed with nitrogen (2×)
  3. customthe reaction was flushed again with nitrogen (2×)
  4. temperaturecooled to room temperature
  5. additiondiluted with water
  6. extractionextracted with EtOAc (2×)
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customPurification of the residue by chromatography on silica gel (5-60% EtOAc in hexanes)

Sources & evidence

ORD record
ord-bba5f5d52ad8430d8debaca0cbbfc127
Source dataset
uspto-grants-2016_03
Patent number
US09290490B2

Reaction notes

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