Dichloromethane → 5-chloro-3-(6-phenylpyridin-3-yl)-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-7-amine

HRID 589192Notes

Reaction equation

HRID 589192 reaction equation
[C:1]1([C:7]2[CH:12]=[CH:11][C:10](B3OC(C)(C)C(C)(C)O3)=[CH:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C(Cl)Cl.[Cl:33][C:34]1[CH:39]=[C:38]([N:40]([CH2:49][O:50][CH2:51][CH2:52][Si:53]([CH3:56])([CH3:55])[CH3:54])[CH2:41][O:42][CH2:43][CH2:44][Si:45]([CH3:48])([CH3:47])[CH3:46])[N:37]2[N:57]=[CH:58][C:59](I)=[C:36]2[N:35]=1>O1CCOCC1.O.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]>[Cl:33][C:34]1[CH:39]=[C:38]([N:40]([CH2:49][O:50][CH2:51][CH2:52][Si:53]([CH3:56])([CH3:55])[CH3:54])[CH2:41][O:42][CH2:43][CH2:44][Si:45]([CH3:48])([CH3:46])[CH3:47])[N:37]2[N:57]=[CH:58][C:59]([C:10]3[CH:9]=[N:8][C:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)=[CH:12][CH:11]=3)=[C:36]2[N:35]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 62657Potassium Phosphate, TribasicHCID 457865262-Phenyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 772312185-chloro-3-iodo-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-7-amine

Product 1

HCID 866647885-chloro-3-(6-phenylpyridin-3-yl)-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-7-amine

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

Substrate 2-phenyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (2.38 mmol, 675 mg), K3PO4 (5.96 mmol, 1264 mg), and PdCl2(dppf).CH2Cl2 (0.20 mmol, 162 mg) were added to a solution of 5-chloro-3-iodo-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-7-amine (1.98 mmol, 1101 mg) in dioxane (18 mL) and H2O (3 mL). The resulting solution was stirred at 70° C. under argon overnight. The mixture was diluted with H2O and then extracted with ethyl acetate (×2). The combined organic layers were washed with brine and dried with Na2SO4. Evaporation and purification by column chromatography afforded 5-chloro-3-(6-phenylpyridin-3-yl)-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-7-amine: LCMS tR=3.36 Min (5 min run, UV254nm). Mass calculated for M+H 582.2, observed LC/MS m/z 582.2 (M+H).

Workup

  1. extractionextracted with ethyl acetate (×2)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried with Na2SO4
  4. customEvaporation and purification by column chromatography

Sources & evidence

ORD record
ord-28c017d28e1946629dafd5989e4bbf74
Source dataset
uspto-grants-2016_01
Patent number
US09227971B2

Reaction notes

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