Potassium Carbonate → 1-[4'-(5-fluoro-2,3-dihydroindole-1-carbonyl)-3,4,5,6-tetrahydro-2H-[1.2']bipyridinyl-4-yl]-1,3-dihydroimidazo[4,5-b]pyridin-2-one

HRID 74621Notes

Reaction equation

HRID 74621 reaction equation
Cl.Cl.[NH:3]1[CH2:8][CH2:7][CH:6]([N:9]2[C:17]3[C:12](=[N:13][CH:14]=[CH:15][CH:16]=3)[NH:11][C:10]2=[O:18])[CH2:5][CH2:4]1.Cl[C:20]1[CH:25]=[C:24]([C:26]([N:28]2[C:36]3[C:31](=[CH:32][C:33]([F:37])=[CH:34][CH:35]=3)[CH2:30][CH2:29]2)=[O:27])[CH:23]=[CH:22][N:21]=1.CCN(C(C)C)C(C)C.C(=O)([O-])[O-].[K+].[K+]>CN1CCCC1=O.O>[F:37][C:33]1[CH:32]=[C:31]2[C:36](=[CH:35][CH:34]=1)[N:28]([C:26]([C:24]1[CH:25]=[CH:20][N:21]=[C:22]([N:3]3[CH2:4][CH2:5][CH:6]([N:9]4[C:17]5[C:12](=[N:13][CH:14]=[CH:15][CH:16]=5)[NH:11][C:10]4=[O:18])[CH2:7][CH2:8]3)[CH:23]=1)=[O:27])[CH2:29][CH2:30]2

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 81531DiisopropylethylamineHCID 222931811-(piperidin-4-yl)-1H,2H,3H-imidazo[4,5-b]pyridin-2-one dihydrochlorideHCID 58386590(2-Chloropyridin-4-yl)-(5-fluoro-2,3-dihydroindol-1-yl)-methanone

Product 1

HCID 426131411-[4'-(5-fluoro-2,3-dihydroindole-1-carbonyl)-3,4,5,6-tetrahydro-2H-[1.2']bipyridinyl-4-yl]-1,3-dihydroimidazo[4,5-b]pyridin-2-one

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
130 °C

Procedure

232 mg (0.8 mmol) 1-piperidin-4-yl-1,3-dihydro-imidazo[4,5-b]pyridin-2-one dihydrochloride were added to 220 mg (0.80 mmol) (2-chloropyridin-4-yl)-(5-fluoro-2,3-dihydro-indol-1-yl)-methanone and 0.52 mL (3.00 mmol) DIPEA in 3.0 mL N-methylpyrrolidone. The reaction mixture was stirred for 6 h at 130° C. After 4 h 400 mg potassium carbonate were added and the reaction mixture was stirred for a further 24 h at 130° C. Then the mixture was poured onto 100 mL water and extracted with EtOAc (3×100 mL). The combined organic phases were dried and evaporated down using the rotary evaporator. The residue was purified by preparative HPLC. The product fractions were combined and evaporated down i. vac. The residue was triturated with 30 mL diethyl ether. The precipitated solid was suction filtered and dried in the air.

Workup

  1. stirringthe reaction mixture was stirred for a further 24 h at 130° C
  2. extractionextracted with EtOAc (3×100 mL)
  3. customThe combined organic phases were dried
  4. customevaporated
  5. customthe rotary evaporator
  6. customThe residue was purified by preparative HPLC
  7. customevaporated down i
  8. customThe residue was triturated with 30 mL diethyl ether
  9. filtrationfiltered
  10. customdried in the air

Sources & evidence

ORD record
ord-fc9cbcb666e14676a9a63819ea78cdfc
Source dataset
uspto-grants-2014_09
Patent number
US08829006B2

Reaction notes

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