Potassium Phosphate, Tribasic → {5-[1-(2-Morpholin-4-yl-ethyl)-1H-pyrazol-4-yl]-thiophen-3-yl}-(octahydro-quinolin-1yl)-methanone formate

HRID 1914559Notes

Reaction equation

HRID 1914559 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.CC1(C)C(C)(C)OB([C:27]2[CH:28]=[N:29][N:30]([CH2:32][CH2:33][N:34]3[CH2:39][CH2:38][O:37][CH2:36][CH2:35]3)[CH:31]=2)[O:21]1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>COCCOC.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:7]([OH:8])=[O:21].[N:34]1([CH2:33][CH2:32][N:30]2[CH:31]=[C:27]([C:2]3[S:6][CH:5]=[C:4]([C:7]([N:9]4[CH:18]5[CH:13]([CH2:14][CH2:15][CH2:16][CH2:17]5)[CH2:12][CH2:11][CH2:10]4)=[O:8])[CH:3]=3)[CH:28]=[N:29]2)[CH2:35][CH2:36][O:37][CH2:38][CH2:39]1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 177499241-(2-Morpholinoethyl)-1H-pyrazole-4-boronic acid pinacol esterHCID 86646712HCID 86646712, compound

Product 1

HCID 66850322{5-[1-(2-Morpholin-4-yl-ethyl)-1H-pyrazol-4-yl]-thiophen-3-yl}-(octahydro-quinolin-1yl)-methanone formateYield 67.9%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
140 °C

Procedure

cis-(5-Bromo-thiophen-3-yl)-(octahydro-quinolin-1-yl)-methanone (0.06 g, 0.18 mmol) was mixed with 4-{2-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrazol-1-yl]-ethyl}-morpholine (0.062 g, 0.2 mmol), tricyclohexylphosphine (0.004 g, 0.01 mmol), potassium phosphate (0.047 g, 0.22 mmol) and tris(dibenzylideneacetone)dipalladium (0) (0.007 g, 0.008 mmol) in DME (2 mL), IMS (0.5 mL) and water (0.25 mL). The reaction mixture was purged with argon then heated by microwave irradiation to 140° C. for 20 minutes. The resultant mixture was diluted with water and extracted with DCM (×2) then the organic phase was dried over sodium sulfate, filtered and the solvent evaporated. The residue was purified by HPLC, eluting with 10%-98% acetonitrile in water (0.1% formic acid) over 20 minutes. The fractions containing the desired product were freeze-dried to give the title compound (0.029 g). LCMS m/z 429.25 [M+H]+ R.T.=7.03 min (Analytical Method 2).

Workup

  1. customThe reaction mixture was purged with argon
  2. additionThe resultant mixture was diluted with water
  3. extractionextracted with DCM (×2)
  4. dry with materialthe organic phase was dried over sodium sulfate
  5. filtrationfiltered
  6. customthe solvent evaporated
  7. customThe residue was purified by HPLC
  8. washeluting with 10%-98% acetonitrile in water (0.1% formic acid) over 20 minutes
  9. additionThe fractions containing the desired product
  10. customwere freeze-dried

Sources & evidence

ORD record
ord-b2a321dab17648a79ee019247f1b7d5a
Source dataset
uspto-grants-2013_12
Patent number
US08614209B2

Reaction notes

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