Sodium Hydroxide → tert-Butyl (1-{4-[2-(2-aminopyridin-3-yl)-5-{3-[(2-hydroxyethyl)amino]phenyl}-3H-imidazo[4,5-b]pyridin-3-yl]phenyl}cyclobutyl)carbamate

HRID 1852939Notes

Reaction equation

HRID 1852939 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.CC1(C)C(C)(C)OB([C:44]2[CH:45]=[C:46]([NH:50][CH2:51][CH2:52][OH:53])[CH:47]=[CH:48][CH:49]=2)O1.[OH-].[Na+]>CN(C=O)C.CCOC(C)=O.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[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:44]4[CH:49]=[CH:48][CH:47]=[C:46]([NH:50][CH2:51][CH2:52][OH:53])[CH:45]=4)=[CH:14][CH:15]=[C:10]3[N:9]=2)=[CH:6][CH:5]=[CH:4][N:3]=1

Participants

7

Reactant 3

HCID 14798Sodium HydroxideHCID 711385082-{[3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]amino}ethanolHCID 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 71142528tert-Butyl (1-{4-[2-(2-aminopyridin-3-yl)-5-{3-[(2-hydroxyethyl)amino]phenyl}-3H-imidazo[4,5-b]pyridin-3-yl]phenyl}cyclobutyl)carbamateYield 86.5%

Reagents, catalysts & solvents 3

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
160 °C

Procedure

A mixture of tert-butyl (1-{4-[2-(2-aminopyridin-3-yl)-5-chloro-3H-imidazo[4,5-b]pyridin-3-yl]phenyl}cyclobutyl)carbamate (70.0 mg, 0.143 mmol), 2-{[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]amino}ethanol (75.0 mg, 0.285 mmol), bis(di-tert-butyl(4-dimethylaminophenyl) phosphine)dichloropalladium(II) (10.1 mg, 0.0143 mmol), and 2M NaOH aq. (0.430 mL, 0.214) in DMF (2 mL) was heated at 160° C. for 1 hour under microwave irradiation. After cooling to room temperature, the mixture was diluted with EtOAc and washed with water (3×) and brine. The combined organic layers were dried over anhydrous Na2SO4 and concentrated. The residue was purified by silica gel column chromatography (CHCl3/EtOAc=1:1→1:2→EtOAc) to afford desired product (73.0 mg, 86.5%) as yellow solid.

Workup

  1. temperatureAfter cooling to room temperature
  2. washwashed with water (3×) and brine
  3. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel column chromatography (CHCl3/EtOAc=1:1→1:2→EtOAc)

Sources & evidence

ORD record
ord-2dbb085c72f948279b39634211074a13
Source dataset
uspto-grants-2015_02
Patent number
US08962619B2

Reaction notes

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