Sodium Bicarbonate → HCID 58456284, compound

HRID 1040036Notes

Reaction equation

HRID 1040036 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-e9867aeb88894a4e80d10ad79aa2ed8f
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Reaction notes

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