Sodium Bicarbonate → HCID 58456284, compound

HRID 410546Notes

Reaction equation

HRID 410546 reaction equation
O[C:2]1([C:13]2[S:14][C:15]([C:18]3[CH:23]=[C:22]([NH:24][C:25]4[N:30]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:28]=[CH:27][N:26]=4)[CH:21]=[C:20]([CH3:35])[CH:19]=3)=[CH:16][N:17]=2)[CH2:7][CH2:6][CH:5]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:4][CH2:3]1.CS(O)(=O)=O.O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.C(=O)(O)[O-].[Na+]>>[CH3:35][C:20]1[CH:19]=[C:18]([C:15]2[S:14][C:13]([C:2]3[CH2:7][CH2:6][CH:5]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:4][CH:3]=3)=[N:17][CH:16]=2)[CH:23]=[C:22]([NH:24][C:25]2[N:30]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:28]=[CH:27][N:26]=2)[CH:21]=1

Participants

4

Reactant 3

HCID 516892Sodium BicarbonateHCID 58456356HCID 58456356, compoundHCID 86584057Phosphorus Pentoxide-Methanesulfonic Acid

Product 1

HCID 58456284HCID 58456284, compoundYield 83.1%

Conditions

Temperature
60 °C

Procedure

To a flask containing ethyl 4-hydroxy-4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]cyclohexanecarboxylate (Example 32, 0.18 g, 0.345 mmol) was added Eaton's Reagent (1.3 mL) and the mixture was heated at 60° C. for 2 hours. The reaction was cooled and added dropwise to saturated sodium bicarbonate. After stirring for 2 minutes, the aqueous solution was extracted three times with ethyl acetate. The combined organics were dried under reduced pressure and purified by silica gel chromatography to yield ethyl 4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]-cyclohex-3-ene-1-carboxylate (0.14 g, 82% yield). MS ESI: [M+H]+ m/z 489.1. 1H NMR (500 MHz, CDCl3) δ 8.65 (d, J=5.2, 1H), 7.96-7.79 (m, 2H), 7.46 (s, 1H), 7.26 (s, 1H), 7.14-6.95 (m, 2H), 6.65 (s, 1H), 4.28-3.96 (m, 2H), 2.90-2.75 (m, 1H), 2.75-2.60 (m, 1H), 2.62-2.47 (m, 3H), 2.39 (s, 3H), 2.26-2.10 (m, 1H), 1.95-1.70 (m, 1H), 1.39-1.17 (m, 3H). rhSYK activity=++

Workup

  1. temperatureThe reaction was cooled
  2. extractionthe aqueous solution was extracted three times with ethyl acetate
  3. customThe combined organics were dried under reduced pressure
  4. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-33fab85b99e64b918a9870e1183fcfd4
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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