Chloroform → HCID 67135749, compound

HRID 2245691Notes

Reaction equation

HRID 2245691 reaction equation
Br[C:2]1[C:3]([CH2:22][OH:23])=[C:4]([N:8]2[CH2:17][CH2:16][C:15]3[C:10](=[CH:11][CH:12]=[C:13]([CH:18]4[CH2:20][CH2:19]4)[CH:14]=3)[C:9]2=[O:21])[CH:5]=[CH:6][CH:7]=1.[CH3:24][N:25]1[C:30]([NH:31][C:32]2[CH:37]=[CH:36][C:35]([C:38]([N:40]3[CH2:45][CH2:44][O:43][CH2:42][CH2:41]3)=[O:39])=[CH:34][CH:33]=2)=[CH:29][C:28](B2OC(C)(C)C(C)(C)O2)=[CH:27][C:26]1=[O:55].C(Cl)(Cl)Cl.O1CCOCC1>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].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.O>[CH:18]1([C:13]2[CH:14]=[C:15]3[C:10](=[CH:11][CH:12]=2)[C:9](=[O:21])[N:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([C:28]4[CH:29]=[C:30]([NH:31][C:32]5[CH:37]=[CH:36][C:35]([C:38]([N:40]6[CH2:41][CH2:42][O:43][CH2:44][CH2:45]6)=[O:39])=[CH:34][CH:33]=5)[N:25]([CH3:24])[C:26](=[O:55])[CH:27]=4)[C:3]=2[CH2:22][OH:23])[CH2:17][CH2:16]3)[CH2:20][CH2:19]1

Participants

8

Reactant 4

HCID 6212ChloroformHCID 312751,4-DioxaneHCID 59216442HCID 59216442, compoundHCID 67135543HCID 67135543, compound

Product 1

HCID 67135749HCID 67135749, compoundYield 53.5%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylCatalystHCID 962WaterSolvent

Procedure

To a flask charged with 2-(3-bromo-2-hydroxymethyl-phenyl)-6-cyclopropyl-3,4-dihydro-2H-isoquinolin-1-one (3.70 g, 9.9 mmol), 1-Methyl-6-[4-(morpholine-4-carbonyl)-phenylamino]-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyridin-2-one (4.38 g, 9.9 mmol), Pd2 (dba)3.CHCl3 (229 mg, 0.25 mmol), 2-Dicyclohexylphosphino-2′,4′,6′-Tri-i-Propyl-1,1′-Biphenyl (238 mg, 0.50 mmol), and K3PO4 hexahydrate (7.5 g, 20 mmol) was added 40 mL of 4:1 dioxane:water and the mixture heated to reflux for 4 h, cooled and filtered over Solka-Floc®, rinsing with ethyl acetate. Partitioned and washed the organic phase with water and brine. Dried over sodium sulfate, filtered and concentrated to afford a dark oil. Purification by silica gel chromatography (methylene chloride/methanol) afforded 3.2 g of 6-Cyclopropyl-2-(2-hydroxymethyl-3-{1-methyl-6-[4-(morpholine-4-carbonyl)-phenylamino]-2-oxo-1,2-dihydro-pyridin-4-yl}-phenyl)-3,4-dihydro-2H-isoquinolin-1-one as a colorless solid. MS (ESI) 606.1 (M+H)+.

Workup

  1. temperatureto reflux for 4 h
  2. temperaturecooled
  3. filtrationfiltered over Solka-Floc®
  4. washrinsing with ethyl acetate
  5. customPartitioned
  6. washwashed the organic phase with water and brine
  7. dry with materialDried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto afford a dark oil
  11. customPurification by silica gel chromatography (methylene chloride/methanol)

Sources & evidence

ORD record
ord-0c7f69de1be849aebbcaa0ae24155fc0
Source dataset
uspto-grants-2010_03
Patent number
US07683064B2

Reaction notes

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