Sodium Carbonate → tert-butyl (1-{4-[2-(2-aminopyridin-3-yl)-5-{3-[4-(dimethylcarbamoyl)piperidin-1-yl]phenyl}-3H-imidazo[4,5-b]pyridin-3-yl]phenyl}cyclobutyl)carbamate

HRID 1852913Notes

Reaction equation

HRID 1852913 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:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[CH2:27][CH2:26][CH2:25]4)=[CH:20][CH:19]=3)[C:11]3=[N:12][C:13](Cl)=[CH:14][CH:15]=[C:10]3[N:9]=2)=[CH:6][CH:5]=[CH:4][N:3]=1.[CH3:36][N:37]([CH3:61])[C:38]([CH:40]1[CH2:45][CH2:44][N:43]([C:46]2[CH:51]=[CH:50][CH:49]=[C:48](B3OC(C)(C)C(C)(C)O3)[CH:47]=2)[CH2:42][CH2:41]1)=[O:39].CC(N)CC1C=CC=CC=1.OP(O)(O)=O.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.O>[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:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[CH2:27][CH2:26][CH2:25]4)=[CH:20][CH:19]=3)[C:11]3=[N:12][C:13]([C:48]4[CH:49]=[CH:50][CH:51]=[C:46]([N:43]5[CH2:44][CH2:45][CH:40]([C:38](=[O:39])[N:37]([CH3:36])[CH3:61])[CH2:41][CH2:42]5)[CH:47]=4)=[CH:14][CH:15]=[C:10]3[N:9]=2)=[CH:6][CH:5]=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 62885Benzeneethanamine, alpha-methyl-, phosphate (1:1)HCID 711388033-[4-(Dimethylcarbamoyl)-1-piperidyl]phenylboronic Acid Pinacol EsterHCID 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 71142509tert-butyl (1-{4-[2-(2-aminopyridin-3-yl)-5-{3-[4-(dimethylcarbamoyl)piperidin-1-yl]phenyl}-3H-imidazo[4,5-b]pyridin-3-yl]phenyl}cyclobutyl)carbamate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
160 °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 (400 mg, 0.81 mmol) in DMF (8.1 mL)/water (0.45 mL), were added N,N-dimethyl-1-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperidine-4-carboxamide. (584 mg, 1.6 mmol), AMPHOS (58 mg, 0.08 mmol) and Na2CO3 (95 mg, 0.9 mmol). The mixture was heated at 160° C. for 1 h in microwave oven. The mixture was evaporated under reduced pressure and the residue was purified with silica gel column chromatography (hexane/ethyl acetate/methanol, 10:0:0 to 0:10:1) to give tert-butyl (1-{4-[2-(2-aminopyridin-3-yl)-5-{3-[4-(dimethylcarbamoyl)piperidin-1-yl]phenyl}-3H-imidazo[4,5-b]pyridin-3-yl]phenyl}cyclobutyl)carbamate. This compound was deprotected with methanol (15 mL) and 4M HCl in ethyl acetate (15 mL) for 18 h at rt. The mixture was solidified with diethyl ether and the solid was purified with HPLC and HCl was added to the fraction and evaporated then solidified with diethyl ether to give the titled compound (281 mg, 50%) as a white solid.

Workup

  1. customThe mixture was evaporated under reduced pressure
  2. customthe residue was purified with silica gel column chromatography (hexane/ethyl acetate/methanol, 10:0:0 to 0:10:1)

Sources & evidence

ORD record
ord-863d52d0b9b74c0fbbb0a9c8396de828
Source dataset
uspto-grants-2015_02
Patent number
US08962619B2

Reaction notes

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