Sodium Carbonate → 4-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)-N-(2-(2-oxo-1,2-dihydropyridin-4-yl)ethyl)benzamide

HRID 1410038Notes

Reaction equation

HRID 1410038 reaction equation
Cl[C:2]1[N:3]=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[C:14]([O:20][CH3:21])[CH:13]=2)[C:5]2[N:10]=[CH:9][S:8][C:6]=2[N:7]=1.[O:22]=[C:23]1[CH:28]=[C:27]([CH2:29][CH2:30][NH:31][C:32](=[O:48])[C:33]2[CH:38]=[CH:37][C:36](B3OC(C)(C)C(C)(C)O3)=[CH:35][CH:34]=2)[CH:26]=[CH:25][NH:24]1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.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>[CH3:21][O:20][C:14]1[CH:13]=[C:12]([NH:11][C:4]2[C:5]3[N:10]=[CH:9][S:8][C:6]=3[N:7]=[C:2]([C:36]3[CH:37]=[CH:38][C:33]([C:32]([NH:31][CH2:30][CH2:29][C:27]4[CH:26]=[CH:25][NH:24][C:23](=[O:22])[CH:28]=4)=[O:48])=[CH:34][CH:35]=3)[N:3]=2)[CH:17]=[CH:16][C:15]=1[O:18][CH3:19]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 68379400N-(2-(2-oxo-1,2-dihydropyridin-4-yl)ethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamideHCID 715341855-chloro-N-(3,4-dimethoxyphenyl)thiazolo[5,4-d]pyrimidin-7-amine

Product 1

HCID 665489584-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)-N-(2-(2-oxo-1,2-dihydropyridin-4-yl)ethyl)benzamideYield 9.2%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

Under N2 atmosphere, 5-chloro-N-(3,4-dimethoxyphenyl)thiazolo[5,4-d]pyrimidin-7-amine (100 mg, 0.31 mmol), N-(2-(2-oxo-1,2-dihydropyridin-4-yl)ethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (140 mg, 0.38 mmol), Pd(PPh3)4 (20 mg, 0.017 mmol) was added in 20 mL of 1,4-dioxane. Na2CO3 (100 mg, 0.94 mmol) in 3 mL of water was added and then the mixture was stirred at reflux for 18 hours. The solvent was removed under reduce pressure and the residue was purified by silica gel chromatography, eluting with DCM/MeOH (20/1) to give 4-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)-N-(2-(2-oxo-1,2-dihydropyridin-4-yl)ethyl)benzamide (15 mg, 9%) as a yellow sold. 1H NMR (300 MHz, DMSO): δ 11.34 (s, 1H), 10.15 (s, 1H), 9.38 (s, 1H), 8.67-8.65 (m, 1H), 8.45 (s, 1H), 8.43 (s, 1H), 7.95-7.81 (m, 3H), 7.51-7.47 (m, 1H), 7.26 (d, 1H, J=6.6 Hz), 7.01 (d, 1H, J=8.7 Hz), 6.15 (s, 1H), 6.08 (d, 1H, J=6.6 Hz), 3.83 (s, 3H), 3.78 (s, 3H), 3.50-3.48 (m, 2H), 2.72-2.65 (m, 2H). LC-MS: 528.9 [M+H]+, tR=1.35 min. HPLC: 98.40% at 214 nm, 99.86% at 254 nm, tR=5.18 min.

Workup

  1. temperatureat reflux for 18 hours
  2. customThe solvent was removed
  3. customthe residue was purified by silica gel chromatography
  4. washeluting with DCM/MeOH (20/1)

Sources & evidence

ORD record
ord-9013612f66f64c93901f050a94609492
Source dataset
uspto-grants-2014_12
Patent number
US08921383B2

Reaction notes

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