Sodium Hydroxide → HCID 71142517, compound

HRID 1914028Notes

Reaction equation

HRID 1914028 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][C@H:37]1[O:42][C@@H:41]([CH3:43])[CH2:40][N:39]([C:44]2[CH:49]=[CH:48][CH:47]=[C:46](B3OC(C)(C)C(C)(C)O3)[CH:45]=2)[CH2:38]1.[OH-].[Na+]>COCCOC.C(Cl)Cl.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[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:46]4[CH:47]=[CH:48][CH:49]=[C:44]([N:39]5[CH2:40][C@H:41]([CH3:43])[O:42][C@H:37]([CH3:36])[CH2:38]5)[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 71138397HCID 71138397, compoundHCID 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 71142517HCID 71142517, compoundYield 44.5%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6344DichloromethaneSolvent2×HCID 80711,2-DimethoxyethaneSolvent

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 (50.0 mg, 0.101 mmol), cis-2,6-dimethyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]morpholine (58.5 mg, 0.153 mmol), Pd(dppf)2Cl2.DCM (8.32 mg, 0.0102 mmol), and 2M NaOH aq. (0.150 mL, 0.310) in DME (2 mL) was heated at 80° C. for 10 hours under nitrogen. After cooling to room temperature, the mixture was diluted with DCM and filtered through a Celite pad. The combined filtrate and washings were concentrated. The residue was purified by silica gel column chromatography (CHCl3/EtOAc=2:1→1:1→1:2) to afford desired product (29.0 mg, 44.1%) as pale yellow foam.

Workup

  1. filtrationfiltered through a Celite pad
  2. concentrationThe combined filtrate and washings were concentrated
  3. customThe residue was purified by silica gel column chromatography (CHCl3/EtOAc=2:1→1:1→1:2)

Sources & evidence

ORD record
ord-a63dbfa0cafa4d69b07622d7d8be733e
Source dataset
uspto-grants-2013_12
Patent number
US08609688B2

Reaction notes

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