Sodium Hydroxide → HCID 71142524, compound

HRID 1852928Notes

Reaction equation

HRID 1852928 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.[CH2:36]([O:43][CH2:44][C@H:45]1[O:50][CH2:49][CH2:48][N:47]([C:51]2[CH:56]=[CH:55][CH:54]=[C:53](B3OC(C)(C)C(C)(C)O3)[CH:52]=2)[CH2:46]1)[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.[OH-].[Na+]>COCCOC.C(Cl)Cl.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:55]4[CH:54]=[CH:53][CH:52]=[C:51]([N:47]5[CH2:48][CH2:49][O:50][C@H:45]([CH2:44][O:43][CH2:36][C:37]6[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=6)[CH2:46]5)[CH:56]=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 71138723HCID 71138723, 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 71142524HCID 71142524, compoundYield 48.3%

Reagents, catalysts & solvents 3

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 6344DichloromethaneSolventHCID 80711,2-DimethoxyethaneSolvent

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 (50.0 mg, 0.101 mmol), (2S)-2-[(benzyloxy)methyl]-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]morpholine (82.4 mg, 0.204 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (7.21 mg, 0.0102 mmol), and 2M NaOH aq. (0.150 mL, 0.310) in DME (2 mL) was heated at 160° C. for 2 hours under microwave irradiation. 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/MeOH=98:2) and PTLC (CHCl3/MeOH=9:1) to afford desired product (36.0 mg, 47.9%) as pale yellow foam.

Workup

  1. temperatureAfter cooling to room temperature
  2. filtrationfiltered through a Celite pad
  3. concentrationThe combined filtrate and washings were concentrated
  4. customThe residue was purified by silica gel column chromatography (CHCl3/MeOH=98:2) and PTLC (CHCl3/MeOH=9:1)

Sources & evidence

ORD record
ord-f276b96235a94de18f805f2b419fd078
Source dataset
uspto-grants-2015_02
Patent number
US08962619B2

Reaction notes

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