Cesium carbonate → HCID 58110350, compound

HRID 1914557Notes

Reaction equation

HRID 1914557 reaction equation
Br[C:2]1[S:6][CH:5]=[C:4]([C:7]([N:9]2[C@@H:18]3[C@@H:13]([CH2:14][CH2:15][CH2:16][CH2:17]3)[CH2:12][CH2:11][CH2:10]2)=[O:8])[CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:25]([O:27][C:28](=[O:44])[CH2:29][N:30]1[CH:34]=[C:33](B2OC(C)(C)C(C)(C)O2)[CH:32]=[N:31]1)[CH3:26]>COCCOC.O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[CH2:25]([O:27][C:28](=[O:44])[CH2:29][N:30]1[CH:34]=[C:33]([C:2]2[S:6][CH:5]=[C:4]([C:7]([N:9]3[CH:18]4[CH:13]([CH2:14][CH2:15][CH2:16][CH2:17]4)[CH2:12][CH2:11][CH2:10]3)=[O:8])[CH:3]=2)[CH:32]=[N:31]1)[CH3:26]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 162183851-(Ethoxycarbonylmethyl)-1H-pyrazole-4-boronic acid pinacol esterHCID 86646712HCID 86646712, compound

Product 1

HCID 58110350HCID 58110350, compoundYield 61.9%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
140 °C

Procedure

cis-(5-Bromo-thiophen-3-yl)-(octahydro-quinolin-1-yl)-methanone (0.217 g, 0.66 mmol) was added to a solution of caesium carbonate (0.32 g, 0.99 mmol), [4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrazol-1-yl]-acetic acid ethyl ester (0.203 g, 0.725 mmol) and palladium tetrakis(triphenylphosphine) (76 mg, 0.07 mmol) in DME (6 mL), IMS (2 mL) and water (1 mL). The reaction mixture was purged with nitrogen and heated by microwave irradiation to 140° C. for 20 minutes then diluted with water and extracted with DCM (×2). The organic solution was dried over sodium sulfate, filtered and the solvent evaporated. The crude material was purified by chromatography on a 5 g silica II cartridge, eluting with 10-50% ethyl acetate in cyclohexane then columned using 0-25% diethyl ether in DCM to afford {4-[4-(octahydro-quinoline-1-carbonyl)-thiophen-2-yl]-pyrazol-1-yl}-acetic acid ethyl ester (164 mg). LCMS m/z 402.41 [M+H]+ R.T.=3.91 min (Analytical Method 6).

Workup

  1. customThe reaction mixture was purged with nitrogen
  2. additionthen diluted with water
  3. extractionextracted with DCM (×2)
  4. dry with materialThe organic solution was dried over sodium sulfate
  5. filtrationfiltered
  6. customthe solvent evaporated
  7. customThe crude material was purified by chromatography on a 5 g silica II cartridge
  8. washeluting with 10-50% ethyl acetate in cyclohexane

Sources & evidence

ORD record
ord-9e13f6b4c58c4533bd8bc7eb4be4b003
Source dataset
uspto-grants-2013_12
Patent number
US08614209B2

Reaction notes

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