Ethanol → HCID 178508666, compound

HRID 855944Notes

Reaction equation

HRID 855944 reaction equation
FC(F)(F)C1C=C([C:13]2[C:14]3[NH:27][CH:26]=[CH:25][C:15]=3[C:16]3[C:21]([CH:22]=2)=[N:20][C:19]([NH2:23])=[N:18][C:17]=3[NH2:24])C=C(C(F)(F)F)C=1.CC1(C)C(C)(C)OB([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=2[CH2:44][CH2:45][C:46]([OH:48])=[O:47])O1.C(=O)([O-])[O-].[Na+].[Na+].C(O)C>CO.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Pd].COCCOC>[NH2:24][C:17]1[C:16]2[C:15]3[CH:25]=[CH:26][NH:27][C:14]=3[C:13]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=3[CH2:44][CH2:45][C:46]([OH:48])=[O:47])=[CH:22][C:21]=2[N:20]=[C:19]([NH2:23])[N:18]=1

Participants

8

Reactant 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 66836784HCID 66836784, compoundHCID 178508667HCID 178508667, compound

Product 1

HCID 178508666HCID 178508666, compoundYield 12.1%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 887MethanolSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
25 °C

Procedure

A mixture of 3-(2-bromo-phenyl)-propionic acid (458 mg, 2.0 mmol), 4,4,5,5,4′,4′,5′,5′-octamethyl-[2,2′]bi[[1,3,2]dioxaborolanyl](558 mg, 2.20 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (II) (132 mg, 0.18 mmol), and potassium acetate (589 mg, 6.0 mmol) was heated to 95° C. for 2 d. The resulting mixture was diluted with water and extracted with ethyl acetate. The combined organic layers were washed with a saturated aqueous sodium chloride solution, filtered through a pad of silca gel and sodium sulfate, and concentrated in vacuo to afford 3-[2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-propionic acid. A solution of 6-iodo-7H-pyrrolo[3,2-f]quinazoline-1,3-diamine (prepared as in Example 1, 100 mg, 0.31 mmol), 3-[2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-propionic acid (102 mg, 0.37 mmol), tetrakis(triphenylphosphine)palladium(o) (71 mg, 0.06 mmol) in a 2.0M aqueous sodium carbonate solution (0.5 mL), ethanol (1.5 mL), and ethylene glycol dimethyl ether (1.5 mL) was heated to 95° C. for 18 h. The resulting mixture was cooled to 25° C., dissolved in methanol and tetrahydrofuran, and filtered through a pad of silica gel and sodium sulfate. The filtrate was concentrated in vacuo. HPLC purification (Shimadzu HPLC, ODSA column from Medchem, 2×10 cm, 10 micro, 10-90% CH3CN/H2O with 0.1% TFA.) afforded 3-[2-(1,3-diamino-7H-pyrrolo[3,2-f]quinazolin-6-yl)-phenyl]-propionic acid (12.5 mg, 12.1%); LRMS for C19H17N5O2 (M+H)+ at m/z=348.

Workup

  1. filtrationtetrahydrofuran, and filtered through a pad of silica gel and sodium sulfate
  2. concentrationThe filtrate was concentrated in vacuo
  3. customHPLC purification (Shimadzu HPLC, ODSA column from Medchem, 2×10 cm, 10 micro, 10-90% CH3CN/H2O with 0.1% TFA.)

Sources & evidence

ORD record
ord-4cc07362783845fc939b4bcf9066fce9
Source dataset
uspto-grants-2007_08
Patent number
US07262297B2

Reaction notes

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