Dimethylformamide → 5-(3-Methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazole-2-carbaldehyde

HRID 1040113Notes

Reaction equation

HRID 1040113 reaction equation
C([N-]C(C)C)(C)C.[Li+].[CH3:9][C:10]1[CH:11]=[C:12]([NH:21][C:22]2[N:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[CH:24][N:23]=2)[CH:13]=[C:14]([C:16]2[S:20][CH:19]=[N:18][CH:17]=2)[CH:15]=1.CN([CH:35]=[O:36])C>C1COCC1.C(OCC)(=O)C>[CH3:9][C:10]1[CH:15]=[C:14]([C:16]2[S:20][C:19]([CH:35]=[O:36])=[N:18][CH:17]=2)[CH:13]=[C:12]([NH:21][C:22]2[N:27]=[C:26]([C:28]([F:29])([F:31])[F:30])[CH:25]=[CH:24][N:23]=2)[CH:11]=1

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 2724682Lithium diisopropylamideHCID 58456403N-[3-methyl-5-(1,3-thiazol-5-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine

Product 1

HCID 866582525-(3-Methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazole-2-carbaldehydeYield 81%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

To a flask was added tetrahydrofuran (60 mL) and the solution was cooled to −78° C. Lithium diisopropylamide (19.8 mL, 35.7 mmol) was added and the mixture was allowed to cool to −78° C. INTERMEDIATE 4 (4.0 g, 11.90 mmol) was dissolved in THF (60 mL) and added in portion. The solution was stirred for 30 minutes. DMF (1.30 g, 17.84 mmol) was dissolved in THF (60 mL) and added over a period of five minutes. The solution was then allowed to warm to room temperature. The reaction mixture was then diluted with ethyl acetate, washed with saturated ammonium chloride, dried over magnesium sulfate, filtered and concentrated. The solid was purified by silica gel column chromatography to yield 5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazole-2-carbaldehyde (3.5 g, 81%). MS ESI: [M+H]+ m/z 364.8. 1H NMR (500 MHz, DMSO-d6) δ 10.36 (s, 1H), 9.91 (s, 1H), 8.86 (d, J=5.3, 1H), 8.57 (s, 1H), 8.19 (s, 1H), 7.54 (s, 1H), 7.38 (s, 1H), 7.31 (d, J=5.2, 1H), 2.35 (s, 3H).

Workup

  1. temperatureto cool to −78° C
  2. additionadded in portion
  3. additionadded over a period of five minutes
  4. temperatureto warm to room temperature
  5. washwashed with saturated ammonium chloride
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe solid was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-a2466a5494ee4370afbc085f70ad08d6
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Reaction notes

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