Sodium Bicarbonate → Quinazoline

HRID 1469108Notes

Reaction equation

HRID 1469108 reaction equation
I[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][N:6]=[C:5]2N1CCC2C(=CC(OC)=CC=2)C1.CC1(C)C(C)(C)OB(C2C=C3C=CN([Si](C(C)C)(C(C)C)C(C)C)C3=NC=2)O1.C(=O)([O-])O.[Na+]>O1CCOCC1.O.CC(=O)OCC.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[N:8]1[C:9]2[C:4](=[CH:3][CH:2]=[CH:11][CH:10]=2)[CH:5]=[N:6][CH:7]=1

Participants

8

Reactant 3

HCID 516892Sodium BicarbonateHCID 457901505-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridineHCID 680263256-iodo-4-(7-methoxy-3,4-dihydro-1H-isoquinolin-2-yl)quinazoline

Product 1

HCID 9210QuinazolineYield 64%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

0.20 g of 6-iodo-4-(7-methoxy-3,4-dihydro-1H-isoquinolin-2-yl)quinazoline, 0.28 g of 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridine, 0.11 g of sodium hydrogencarbonate and 0.03 g of Pd(PPh3)2Cl2 in 5.00 ml of dioxane and 0.50 ml of water are heated at 90° C. under nitrogen in a flask until the reaction is complete (HPLC check, about 5 hours). The cooled reaction solution is diluted with EA and washed 3 times with water. The organic phase is dried over sodium sulfate and purified by means of column chromatography (gradient EA: methanol 5-30% in 13 min), giving 0.20 g of 4-(7-methoxy-3,4-dihydro-1H-isoquinolin-2-yl)-6-[2-methyl-3-[(2-trimethylsilanylethoxymethyl)-3H-imidazo]4,5-b]pyridin-6-yl]quinazoline as white powder (yield 64%, content 79%); MS-FAB (M+H+)=553.3; Rf (polar method): 2.14 min.

Workup

  1. custom(HPLC check, about 5 hours)
  2. customThe cooled reaction solution
  3. washwashed 3 times with water
  4. dry with materialThe organic phase is dried over sodium sulfate
  5. custompurified by means of column chromatography (gradient EA: methanol 5-30% in 13 min)

Sources & evidence

ORD record
ord-00e90dffc05f4ac79a2124014f704980
Source dataset
uspto-grants-2015_04
Patent number
US09006255B2

Reaction notes

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