Dichloromethane → HCID 86686735, compound

HRID 2369014Notes

Reaction equation

HRID 2369014 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([N:8]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[CH2:9][O:10][CH2:11][CH2:12][Si:13]([CH3:16])([CH3:15])[CH3:14])[N:5]2[N:25]=[CH:26][C:27](I)=[C:4]2[N:3]=1.[F:29][C:30]1[CH:31]=[C:32]2[C:37](=[CH:38][CH:39]=1)[N:36]=[CH:35][C:34](B1OC(C)(C)C(C)(C)O1)=[CH:33]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>[Cl:1][C:2]1[CH:7]=[C:6]([N:8]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[CH2:9][O:10][CH2:11][CH2:12][Si:13]([CH3:16])([CH3:15])[CH3:14])[N:5]2[N:25]=[CH:26][C:27]([C:34]3[CH:35]=[N:36][C:37]4[C:32]([CH:33]=3)=[CH:31][C:30]([F:29])=[CH:39][CH:38]=4)=[C:4]2[N:3]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 66584499HCID 66584499, compoundHCID 772312185-chloro-3-iodo-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-7-amine

Product 1

HCID 86686735HCID 86686735, compoundYield 73%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
40 °C

Procedure

To 5-chloro-3-iodo-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-7-amine (example 19, step 1, 2.50 g, 4.52 mmol) was added 6-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinoline (2.05 g, 4.52 mmol), K2CO3 (1.87 g, 13.56 mmol), PdCl2(dppf).CH2Cl2 (0.37 g, 0.45 mmol), dioxane (36 mL) and H2O (9 mL). The resulting mixture was heated at 40° C. for 16 hours, at which time LC/MS analysis confirmed full consumption of starting material. On cooling, H2O (20 mL) and CH2Cl2 (50 mL) were used to transfer the reaction mixture to a separatory funnel. Brine (30 mL) was added and organics were extracted with CH2Cl2 (4×50 mL), dried (Na2SO4) and concentrated in vacuo to give a black oil. Gradient column chromatography on silica eluting with 10% to 30% EtOAc/hexanes gave 5-chloro-3-(6-fluoroquinolin-3-yl)-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-7-amine as a light yellow solid (1.89 g, 3.30 mmol, 73%). LC/MS: 3.22 mins, m/z=574.2 (MH+).

Workup

  1. customconsumption of starting material
  2. temperatureOn cooling
  3. additionBrine (30 mL) was added
  4. extractionorganics were extracted with CH2Cl2 (4×50 mL)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customto give a black oil

Sources & evidence

ORD record
ord-96144bd48e394813ade0232c561b4b68
Source dataset
uspto-grants-2014_04
Patent number
US08703784B2

Reaction notes

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