Dichloromethane → HCID 66738932, compound

HRID 2047188Notes

Reaction equation

HRID 2047188 reaction equation
C[O:2][C:3](=[O:20])[CH2:4][C:5]1[CH:10]=[CH:9][C:8](B2OC(C)(C)C(C)(C)O2)=[CH:7][CH:6]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C(Cl)Cl.Cl[C:33]1[CH:38]=[C:37]([N:39](COCC[Si](C)(C)C)COCC[Si](C)(C)C)[N:36]2[N:56]=[CH:57][C:58]([C:59]3[CH:60]=[N:61][C:62]4[C:67]([CH:68]=3)=[CH:66][CH:65]=[CH:64][CH:63]=4)=[C:35]2[N:34]=1>O1CCOCC1.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]>[NH2:39][C:37]1[N:36]2[N:56]=[CH:57][C:58]([C:59]3[CH:60]=[N:61][C:62]4[C:67]([CH:68]=3)=[CH:66][CH:65]=[CH:64][CH:63]=4)=[C:35]2[N:34]=[C:33]([C:8]2[CH:7]=[CH:6][C:5]([CH2:4][C:3]([OH:2])=[O:20])=[CH:10][CH:9]=2)[CH:38]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 62657Potassium Phosphate, TribasicHCID 11219601Methyl 2-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]acetateHCID 86664780(5-Chloro-3-quinolin-3-yl-pyrazolo[1,5-a]pyrimidin-7-yl)-bis-(2-trimethylsilanyl-ethoxymethyl)-amine

Product 1

HCID 66738932HCID 66738932, compoundYield 62%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

[4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-acetic acid methyl ester (0.576 mmol, 160 mg), K3PO4 (0.864 mmol, 183 mg), and PdCl2(dppf).CH2Cl2 (0.029 mmol, 24 mg) was added to a solution of (5-Chloro-3-quinolin-3-yl-pyrazolo[1,5-a]pyrimidin-7-yl)-bis-(2-trimethylsilanyl-ethoxymethyl)-amine (0.288 mmol, 160 mg) in dioxane (2 mL). To this suspension was added distilled H2O (0.2 mL). The resulting solution was stirred at 100° C. under an argon atmosphere for 18 hours. The reaction mixture was concentrated in vacuo. The crude mixture was dissolved in 2:1 MeOH:H2O (1.5 mL) and was treated with 2N NaOH(aq) (1.0 mL). The resulting solution was stirred at room temperature for 18 hours. Aqueous hydrochloride solution (1.0 N, 4 ml) was added to the reaction mixture and the resulting solution was stirred at 65° C. for 2 h. The reaction mixture was concentrated and purified by prep-LC to afford the title compound (70 mg, 62% yield): LC/MS RT=3.21 min. Mass calculated for, M+H 396.14, observed 396.14.

Workup

  1. additionTo this suspension was added
  2. distillationdistilled H2O (0.2 mL)
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. dissolutionThe crude mixture was dissolved in 2:1 MeOH
  5. additionH2O (1.5 mL) and was treated with 2N NaOH(aq) (1.0 mL)
  6. stirringThe resulting solution was stirred at room temperature for 18 hours
  7. additionAqueous hydrochloride solution (1.0 N, 4 ml) was added to the reaction mixture
  8. stirringthe resulting solution was stirred at 65° C. for 2 h
  9. concentrationThe reaction mixture was concentrated
  10. custompurified by prep-LC

Sources & evidence

ORD record
ord-17a7ecf7e220445e9809ea6428ddce00
Source dataset
uspto-grants-2013_11
Patent number
US08591943B2

Reaction notes

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