Potassium Phosphate, Tribasic → Ethyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(6-phenylpyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-1-methylcyclohex-3-enecarboxylate

HRID 1913269Notes

Reaction equation

HRID 1913269 reaction equation
Cl[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:28]3[CH:29]=[N:30][C:31]([C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=4)=[CH:32][CH:33]=3)=[C:4]2[N:3]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH3:48][C:49]1([C:64]([O:66][CH2:67][CH3:68])=[O:65])[CH2:54][CH2:53][C:52](B2OC(C)(C)C(C)(C)O2)=[CH:51][CH2:50]1>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].O1CCOCC1>[CH3:14][Si:13]([CH3:16])([CH3:15])[CH2:12][CH2:11][O:10][CH2:9][N:8]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[C:6]1[N:5]2[N:25]=[CH:26][C:27]([C:28]3[CH:29]=[N:30][C:31]([C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=4)=[CH:32][CH:33]=3)=[C:4]2[N:3]=[C:2]([C:52]2[CH2:53][CH2:54][C:49]([CH3:48])([C:64]([O:66][CH2:67][CH3:68])=[O:65])[CH2:50][CH:51]=2)[CH:7]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 66583732Ethyl 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohex-3-ene-1-carboxylateHCID 866647885-chloro-3-(6-phenylpyridin-3-yl)-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-7-amine

Product 1

HCID 66583831Ethyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(6-phenylpyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-1-methylcyclohex-3-enecarboxylateYield 88.2%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
90 °C

Procedure

To a 40 mL vial charged with 5-chloro-3-(6-phenylpyridin-3-yl)-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-7-amine (Int-18e, 582 mg, 1.0 mmol), Pd(dppf)Cl2 (82 mg, 0.1 mmol), K3PO4 (636 mg, 3.0 mmol), and ethyl 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohex-3-enecarboxylate (441 mg, 1.5 mmol) was added dioxane (20 mL including 1 mL water). The mixture was thoroughly degassed by alternately evacuating the flask under vacuum, then placing it under an argon atmosphere numerous times. The reaction was then heated to 90° C. and stirred overnight. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate (30 mL) and filtered through celite. The solvent was removed under reduced pressure and the residue was purified with column (silica gel, 0-30% ethyl acetate in hexane) gave ethyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(6-phenylpyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-1-methylcyclohex-3-enecarboxylate (Int-18f) (630 mg). HPLC-MS tR=2.89 min (UV254 nm); mass calculated for formula C39H55N5O4Si2 713.4, observed LCMS m/z 714.4 (M+H).

Workup

  1. customThe mixture was thoroughly degassed
  2. customby alternately evacuating the flask under vacuum
  3. temperatureAfter cooling to room temperature
  4. additionthe reaction mixture was diluted with ethyl acetate (30 mL)
  5. filtrationfiltered through celite
  6. customThe solvent was removed under reduced pressure
  7. customthe residue was purified with column (silica gel, 0-30% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-aea79dd0f2d64781b95ffd98e491739e
Source dataset
uspto-grants-2013_12
Patent number
US08609675B2

Reaction notes

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