Sodium Bicarbonate → HCID 178437397, compound

HRID 1469113Notes

Reaction equation

HRID 1469113 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.[CH2:22]([C:24]1[NH:41][C:27]2=[N:28][CH:29]=[C:30](B3OC(C)(C)C(C)(C)O3)[CH:31]=[C:26]2[N:25]=1)[CH3:23].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:30]3[CH:31]=[C:26]4[N:25]=[C:24]([CH2:22][CH3:23])[NH:41][C:27]4=[N:28][CH:29]=3)[CH:19]=2)[N:14]=[CH:13][N:12]=1

Participants

8

Reactant 3

HCID 516892Sodium BicarbonateHCID 67516832HCID 67516832, compoundHCID 178437390HCID 178437390, compound

Product 1

HCID 178437397HCID 178437397, compoundYield 92%

Reagents, catalysts & solvents 4

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

Procedure

0.25 g of 4-(3,4-dihydro-1H-isoquinolin-2-yl)-6-iodoquinazoline, 0.35 g of 2-ethyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-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 0-45% in 16 min), giving 0.05 g of 4-(3,4-dihydro-1H-isoquinolin-2-yl)-6-(2-ethyl-3H-imidazo[4,5-b]pyridin-6-yl)quinazoline (“A10”) as white powder (yield 92%, content 94%); MS-FAB (M+H+)=407.2; Rf (polar method): 1.40 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 0-45% in 16 min)

Sources & evidence

ORD record
ord-8aa4f4ae4a97405a942a98212c7333fb
Source dataset
uspto-grants-2015_04
Patent number
US09006255B2

Reaction notes

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