Iodide Ion → 4-(1,3-dihydroisoindol-2-yl)-6-(1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-5-yl)quinazoline

HRID 1469089Notes

Reaction equation

HRID 1469089 reaction equation
[CH2:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][N:2]1[C:10]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17](I)[CH:18]=2)[N:13]=[CH:12][N:11]=1.CC1(C)C(C)(C)OB([C:29]2[CH:30]=[C:31]3[CH:37]=[CH:36][N:35]([Si:38]([CH:45]([CH3:47])[CH3:46])([CH:42]([CH3:44])[CH3:43])[CH:39]([CH3:41])[CH3:40])[C:32]3=[N:33][CH:34]=2)O1.C(=O)([O-])O.[Na+].[I-]>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>[CH2:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][N:2]1[C:10]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([C:29]3[CH:30]=[C:31]4[CH:37]=[CH:36][N:35]([Si:38]([CH:42]([CH3:44])[CH3:43])([CH:45]([CH3:47])[CH3:46])[CH:39]([CH3:40])[CH3:41])[C:32]4=[N:33][CH:34]=3)[CH:18]=2)[N:13]=[CH:12][N:11]=1

Participants

9

Reactant 4

HCID 30165Iodide IonHCID 516892Sodium BicarbonateHCID 457901505-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridineHCID 675144384-(1,3-Dihydroisoindol-2-yl)-6-iodoquinazoline

Product 1

HCID 675137734-(1,3-dihydroisoindol-2-yl)-6-(1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-5-yl)quinazolineYield 34.5%

Reagents, catalysts & solvents 4

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

Procedure

0.25 g of 4-(1,3-dihydroisoindol-2-yl)-6-iodoquinazoline, 0.32 g of 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]-pyridine, 0.16 g of sodium hydrogencarbonate and 0.09 g of PdCl2(PPh3)2 in 5.00 ml of dioxane and 0.50 ml of water are heated at 90° C. under nitrogen in a flask until the iodide has reacted completely (HPLC check, about 8 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 heptane: EA 5-100% in 30 min), giving 0.12 g of 4-(1,3-dihydroisoindol-2-yl)-6-(1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-5-yl)quinazoline as slightly beige solid (yield 33%, content 95%); MS-FAB (M+H+)=520.0; Rf (polar method): 2.77 min.

Workup

  1. customhas reacted completely (HPLC check, about 8 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 heptane: EA 5-100% in 30 min)

Sources & evidence

ORD record
ord-58bdf58d3b68436a86e67134f08da223
Source dataset
uspto-grants-2015_04
Patent number
US09006255B2

Reaction notes

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