Chloroform → HCID 59244926, compound

HRID 912187Notes

Reaction equation

HRID 912187 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5](I)=[CH:4][N:3]=1.[CH3:9][O:10][C:11]1[CH:48]=[CH:47][C:14]([CH2:15][N:16]([CH2:38][C:39]2[CH:44]=[CH:43][C:42]([O:45][CH3:46])=[CH:41][CH:40]=2)[C:17]2[N:22]=[CH:21][C:20]([C:23]3[C:24]4[CH2:37][CH2:36][NH:35][C:25]=4[N:26]=[C:27]([N:29]4[CH2:34][CH2:33][O:32][CH2:31][CH2:30]4)[N:28]=3)=[CH:19][N:18]=2)=[CH:13][CH:12]=1.C(Cl)(Cl)Cl.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>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].C1(C)C=CC=CC=1>[Cl:1][C:2]1[N:3]=[CH:4][C:5]([N:35]2[C:25]3[N:26]=[C:27]([N:29]4[CH2:30][CH2:31][O:32][CH2:33][CH2:34]4)[N:28]=[C:23]([C:20]4[CH:21]=[N:22][C:17]([N:16]([CH2:38][C:39]5[CH:44]=[CH:43][C:42]([O:45][CH3:46])=[CH:41][CH:40]=5)[CH2:15][C:14]5[CH:47]=[CH:48][C:11]([O:10][CH3:9])=[CH:12][CH:13]=5)=[N:18][CH:19]=4)[C:24]=3[CH2:37][CH2:36]2)=[CH:6][CH:7]=1

Participants

9

Reactant 5

HCID 6212ChloroformHCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 43971762-Chloro-5-iodopyridineHCID 45258862Bis-(4-methoxybenzyl)-[5-(2-morpholin-4-yl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl)-pyrimidin-2-yl]-amine

Product 1

HCID 59244926HCID 59244926, compoundYield 36.7%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A toluene solution (10 ml) of 2-chloro-5-iodopyridine (67 mg, 0.27 mmol), bis-(4-methoxy-benzyl)-[5-(2-morpholin-4-yl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl)-pyrimidin-2-yl]-amine (100 mg, 0.18 mmol), Pd2(dba)3.CHCl3 (19 mg, 0.018 mmol), BINAP (17 mg, 0.02 mmol) and cesium carbonate (181 mg, 0.55 mmol) was degassed under ultrasonic irradiation, followed by stirring at 100° C. for 14 hours under a nitrogen atmosphere. The reaction mixture was cooled to room temperature, and diluted with water, followed by extraction with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate, and subsequently magnesium sulfate was filtered off. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate=3/1), to obtain {5-[7-(6-chloro-pyridin-3-yl)-2-morpholin-4-yl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl]-pyrimidin-2-yl}-bis-(4-methoxy-benzyl)-amine as a yellow solid (43 mg, 36%).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe organic layer was washed with saturated aqueous sodium chloride solution
  4. dry with materialdried over magnesium sulfate, and subsequently magnesium sulfate
  5. filtrationwas filtered off
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customthe residue was purified by silica gel column chromatography (hexane/ethyl acetate=3/1)

Sources & evidence

ORD record
ord-bfdf80fe94b841479097700466420d86
Source dataset
uspto-grants-2011_09
Patent number
US08022205B2

Reaction notes

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