N-{3-[2-(3,6-dihydro-2H-thiopyran-4-yl)-1,3-thiazol-5-yl]-5-methylphenyl}-4-(trifluoromethyl)pyrimidin-2-amine → HCID 58456143, compound

HRID 1040176Notes

Reaction equation

HRID 1040176 reaction equation
[S:1]1[CH2:6][CH:5]=[C:4]([C:7]2[S:8][C:9]([C:12]3[CH:13]=[C:14]([NH:19][C:20]4[N:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[CH:22][N:21]=4)[CH:15]=[C:16]([CH3:18])[CH:17]=3)=[CH:10][N:11]=2)[CH2:3][CH2:2]1>CCOC(C)=O.[Pd]>[CH3:18][C:16]1[CH:15]=[C:14]([NH:19][C:20]2[N:25]=[C:24]([C:26]([F:29])([F:27])[F:28])[CH:23]=[CH:22][N:21]=2)[CH:13]=[C:12]([C:9]2[S:8][C:7]([CH:4]3[CH2:3][CH2:2][S:1][CH2:6][CH2:5]3)=[N:11][CH:10]=2)[CH:17]=1

Participants

4

Reactant 1

HCID 58456228N-{3-[2-(3,6-dihydro-2H-thiopyran-4-yl)-1,3-thiazol-5-yl]-5-methylphenyl}-4-(trifluoromethyl)pyrimidin-2-amine

Product 1

HCID 58456143HCID 58456143, compoundYield 48%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalyst2×HCID 8857Ethyl AcetateSolvent

Procedure

N-{3-[2-(3,6-dihydro-2H-thiopyran-4-yl)-1,3-thiazol-5-yl]-5-methylphenyl}-4-(trifluoromethyl)pyrimidin-2-amine (Example 133, 85 mg, 0.196 mmol) was dissolved in EtOAc (5 ml) and flushed with nitrogen (3×). Palladium on carbon (20.8 mg, 0.020 mmol) was added, and the reaction was flushed with hydrogen (3×) via a hydrogen balloon. The reaction was stirred at room temperature for 16 hrs under hydrogen atmosphere. A further aliquot of palladium on carbon (208 mg, 0.196 mmol) was added, the reaction was purged again with hydrogen, and stirred under hydrogen atmosphere for additional 72 hrs. The reaction mixture was subsequently filtered through a pad of Celite and concentrated under reduced pressure. Column chromatography on silica (gradient elution, 0 to 50% EtOAc in hexanes) afforded N-{3-methyl-5-[2-(tetrahydro-2H-thiopyran-4-yl)-1,3-thiazol-5-yl]phenyl}-4-(trifluoromethyl)pyrimidin-2-amine (0.041 g, 0.094 mmol, 48% yield) as a colorless foam. MS ESI: [M+H]+ m/z 437.0. 1H NMR (500 MHz, DMSO-d6) δ 10.26 (s, 1H), 8.83 (d, J=4.9, 1H), 7.96 (m, 2H), 7.42 (bs, 1H), 7.28 (d, J=4.9, 1H), 7.18 (bs, 1H), 3.15 (m, 2H), 2.80 (m, 1H), 2.68 (m, 2H), 2.48 (m, 5H), 1.92 (m, 2H). rhSYK activity=+++.

Workup

  1. customflushed with nitrogen (3×)
  2. customthe reaction was flushed with hydrogen (3×) via a hydrogen balloon
  3. customthe reaction was purged again with hydrogen
  4. stirringstirred under hydrogen atmosphere for additional 72 hrs
  5. filtrationThe reaction mixture was subsequently filtered through a pad of Celite
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-9a5fa44c734b49ae83d335744f36b263
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Reaction notes

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