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

HRID 1410043Notes

Reaction equation

HRID 1410043 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.[CH3:22][N:23]1[CH:28]=[CH:27][C:26]([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:25][C:24]1=[O:49].C([O-])([O-])=O.[Na+].[Na+]>O.O1CCOCC1.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:26]4[CH:27]=[CH:28][N:23]([CH3:22])[C:24](=[O:49])[CH:25]=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 68379549HCID 68379549, compoundHCID 715341855-chloro-N-(3,4-dimethoxyphenyl)thiazolo[5,4-d]pyrimidin-7-amine

Product 1

HCID 665489594-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)-N-(2-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)ethyl)benzamideYield 12%

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 (150 mg, 0.47 mmol), N-(2-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)ethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (220 mg, crude), Pd(PPh3)4 (40 mg, 0.035 mmol) and Na2CO3 (100 mg, 0.94 mmol) in 3 mL of water was added in 30 mL of 1,4-dioxane. 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, v/v) to give 4-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)-N-(2-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)ethyl)benzamide (30 mg, 12%) as a yellow sold. 1H NMR (300 MHz, CD3OD): δ 9.13 (s, 1H), 8.52-8.50 (m, 2H), 7.89-7.80 (m, 3H), 7.58 (d, 1H, J=6.9 Hz), 7.40 (dd, 1H, J1=8.4 Hz, J2=2.4 Hz), 7.03 (d, 1H, J=8.7 Hz), 6.46 (s, 1H), 6.38 (dd, 1H, J1=6.6 Hz, J2=1.8 Hz), 3.94 (s, 3H), 3.88 (s, 3H), 3.66 (t, 2H, J=7.0 Hz), 3.54 (s, 3H), 2.84 (t, 2H, J=7.0 Hz). LC-MS: 543 [M+H]+, 541 [M−H]−, tR=1.37 min. HPLC: 100% at 214 nm, 100% at 254 nm, tR=5.36 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-6070874376c245d6a2312d5be9d7b36a
Source dataset
uspto-grants-2014_12
Patent number
US08921383B2

Reaction notes

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