Dichloromethane → HCID 66584551, compound

HRID 2369011Notes

Reaction equation

HRID 2369011 reaction equation
I[C:2]1[CH:3]=[N:4][N:5]2[C:10]([N:11]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25])[CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])=[CH:9][C:8]([CH:28]([NH:30][CH:31]3[CH2:36][CH2:35][O:34][CH2:33][CH2:32]3)[CH3:29])=[N:7][C:6]=12.B(O)O.[F:40][C:41]1[CH:42]=[C:43]2[C:48](=[CH:49][CH:50]=1)[N:47]=[CH:46][CH:45]=[CH:44]2.C([O-])([O-])=O.[K+].[K+].C(Cl)Cl>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O.O1CCOCC1>[F:40][C:41]1[CH:42]=[C:43]2[C:48](=[CH:49][CH:50]=1)[N:47]=[CH:46][C:45]([C:2]1[CH:3]=[N:4][N:5]3[C:10]([N:11]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25])[CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])=[CH:9][C:8]([CH:28]([NH:30][CH:31]4[CH2:36][CH2:35][O:34][CH2:33][CH2:32]4)[CH3:29])=[N:7][C:6]=13)=[CH:44]2

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 66584820HCID 66584820, compoundHCID 178505454HCID 178505454, compound

Product 1

HCID 66584551HCID 66584551, compoundYield 60%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To 3-iodo-5-(1-(tetrahydro-2H-pyran-4-ylamino)ethyl)-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-7-amine (0.14 g, 0.21 mmol) was added 6-fluoroquinoline boronate (0.11 g, 0.42 mmol), K2CO3 (87 mg, 0.63 mmol), PdCl2(dppf).CH2Cl2 (18 mg, 0.02 mmol), dioxane (4 ml) and H2O (1 ml). The resulting mixture was heated at 100° C. for 2 hours, at which time LC/MS analysis confirmed full consumption of starting material. On cooling, the solvent was rotoevaporated, and the crude was redissolved in DCM (40 ml), washed with water (1×5 ml), brine (1×5 ml), dried over MgSO4. Solvent was removed in vacuo and the residue was purified by column chromatography on silica gel. Elution with MeOH/EtOAC (0-20%) gave desired product, 3-(6-fluoroquinolin-3-yl)-5-(1-(tetrahydro-2H-pyran-4-ylamino)ethyl)-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-7-amine (84 mg, 60%).

Workup

  1. customconsumption of starting material
  2. temperatureOn cooling
  3. dissolutionthe crude was redissolved in DCM (40 ml)
  4. washwashed with water (1×5 ml), brine (1×5 ml)
  5. dry with materialdried over MgSO4
  6. customSolvent was removed in vacuo
  7. customthe residue was purified by column chromatography on silica gel
  8. washElution with MeOH/EtOAC (0-20%)

Sources & evidence

ORD record
ord-5c29257c6e0f4182bb295cc2339ccf6f
Source dataset
uspto-grants-2014_04
Patent number
US08703784B2

Reaction notes

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