Sodium Bicarbonate → HCID 67517091, compound

HRID 1469101Notes

Reaction equation

HRID 1469101 reaction equation
[CH2:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][N:2]1[C:11]1[C:20]2[C:15](=[CH:16][CH:17]=[C:18](I)[CH:19]=2)[N:14]=[CH:13][N:12]=1.[CH3:22][C:23]1[N:40]([CH2:41][O:42][CH2:43][CH2:44][Si:45]([CH3:48])([CH3:47])[CH3:46])[C:26]2=[N:27][CH:28]=[C:29](B3OC(C)(C)C(C)(C)O3)[CH:30]=[C:25]2[N:24]=1.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>[CH2:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][N:2]1[C:11]1[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([C:29]3[CH:30]=[C:25]4[N:24]=[C:23]([CH3:22])[N:40]([CH2:41][O:42][CH2:43][CH2:44][Si:45]([CH3:46])([CH3:48])[CH3:47])[C:26]4=[N:27][CH:28]=3)[CH:19]=2)[N:14]=[CH:13][N:12]=1

Participants

8

Reactant 3

HCID 516892Sodium BicarbonateHCID 57685395HCID 57685395, compoundHCID 67516832HCID 67516832, compound

Product 1

HCID 67517091HCID 67517091, compoundYield 72.4%

Reagents, catalysts & solvents 4

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

Procedure

0.87 g of 4-(3,4-dihydro-1H-isoquinolin-2-yl)-6-iodoquinazoline, 0.96 g of 2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-(2-trimethylsilanylethoxymethyl)-3H-imidazo[4,5-b]pyridine, 0.52 g of sodium hydrogencarbonate and 0.29 g of Pd(PPh3)2Cl2 in 17 ml of dioxane and 2 ml of water are heated at 90° C. under nitrogen in a flask until the reaction is complete (HPLC check, about 3 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 0-30% in 20 min), giving 0.85 g of 4-(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 60%, content 86%); MS-FAB (M+H+)=523.2; Rf (polar method): 2.12 min.

Workup

  1. custom(HPLC check, about 3 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 0-30% in 20 min)

Sources & evidence

ORD record
ord-639189c8b288497f80a7a0dd8a1e233f
Source dataset
uspto-grants-2015_04
Patent number
US09006255B2

Reaction notes

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