Sodium Bicarbonate → 3-{3-[4-(1-aminocyclobutyl)phenyl]-5-(3-azetidin-1-ylphenyl)-3H-imidazo[4,5-b]pyridin-2-yl}pyridin-2-amine hydro chloride

HRID 1888011Notes

Reaction equation

HRID 1888011 reaction equation
[NH2:1][C:2]1[C:7]([C:8]2[N:17]([C:18]3[CH:23]=[CH:22][C:21]([C:24]4([NH:28]C(=O)OC(C)(C)C)[CH2:27][CH2:26][CH2:25]4)=[CH:20][CH:19]=3)[C:11]3=[N:12][C:13]([Cl:16])=[CH:14][CH:15]=[C:10]3[N:9]=2)=[CH:6][CH:5]=[CH:4][N:3]=1.CC1(C)C(C)(C)OB([C:44]2[CH:45]=[C:46]([N:50]3[CH2:53][CH2:52][CH2:51]3)[CH:47]=[CH:48][CH:49]=2)O1.C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1.C(O)C.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[ClH:16].[NH2:28][C:24]1([C:21]2[CH:20]=[CH:19][C:18]([N:17]3[C:11]4=[N:12][C:13]([C:44]5[CH:49]=[CH:48][CH:47]=[C:46]([N:50]6[CH2:53][CH2:52][CH2:51]6)[CH:45]=5)=[CH:14][CH:15]=[C:10]4[N:9]=[C:8]3[C:7]3[C:2]([NH2:1])=[N:3][CH:4]=[CH:5][CH:6]=3)=[CH:23][CH:22]=2)[CH2:27][CH2:26][CH2:25]1

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 583451801-(3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)azetidineHCID 86675348tert-butyl (1-(4-(2-(2-aminopyridin-3-yl)-5-chloro-3H-imidazo[4,5-b]pyridin-3-yl)phenyl)cyclobutyl)carbamate

Product 1

HCID 867619933-{3-[4-(1-aminocyclobutyl)phenyl]-5-(3-azetidin-1-ylphenyl)-3H-imidazo[4,5-b]pyridin-2-yl}pyridin-2-amine hydro chlorideYield 8%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 21863594Toluene ethanolSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of tert-butyl (1-{4-[2-(2-aminopyridin-3-yl)-5-chloro-3H-imidazo[4,5-b]pyridin-3-yl]phenyl}cyclobutyl)carbamate (75 mg, 0.15 mmol) in toluene/ethanol (3 ml each), were added 1-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]azetidine (79 mg, 0.31 mmol), Pd(PPh3)4 (9 mg), and saturated sodium bicarbonate in water (300 ul). The reaction was degassed and heated to 100° C. for 18 hr under nitrogen gas. The mixture was poured to water, extracted with ethyl acetate (15 mL×3). The combined organic layer was dried over anhydrous sodium sulfate and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate: methanol=9:1:0.1 to 1:1:0.1) and again purified with HPLC (acetonitrile/water (0.05% formic acid), gradient, 25 ml/min) to give the product (6 mg, 8%). LCMS: 488 [M+H].

Workup

  1. customThe reaction was degassed
  2. additionThe mixture was poured to water
  3. extractionextracted with ethyl acetate (15 mL×3)
  4. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
  5. customevaporated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate: methanol=9:1:0.1 to 1:1:0.1)
  7. customagain purified with HPLC (acetonitrile/water (0.05% formic acid), gradient, 25 ml/min)

Sources & evidence

ORD record
ord-d59d96e978134a39bd41c433e608cd0a
Source dataset
uspto-grants-2013_08
Patent number
US08501770B2

Reaction notes

Loading…