Potassium Carbonate → 3-chloro-N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)propanamide

HRID 1842825Notes

Reaction equation

HRID 1842825 reaction equation
[CH3:1][N:2]([CH3:33])[CH2:3][CH2:4][N:5]([CH3:32])[C:6]1[C:7]([NH2:31])=[CH:8][C:9]([NH:14][C:15]2[N:20]=[C:19]([C:21]3[C:29]4[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=4)[N:23]([CH3:30])[CH:22]=3)[CH:18]=[CH:17][N:16]=2)=[C:10]([O:12][CH3:13])[CH:11]=1.C([O-])([O-])=O.[K+].[K+].[Cl:40][CH2:41][CH2:42][C:43](Cl)=[O:44].[OH-].[Na+]>CC(C)=O.CO>[Cl:40][CH2:41][CH2:42][C:43]([NH:31][C:7]1[CH:8]=[C:9]([NH:14][C:15]2[N:20]=[C:19]([C:21]3[C:29]4[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=4)[N:23]([CH3:30])[CH:22]=3)[CH:18]=[CH:17][N:16]=2)[C:10]([O:12][CH3:13])=[CH:11][C:6]=1[N:5]([CH2:4][CH2:3][N:2]([CH3:1])[CH3:33])[CH3:32])=[O:44]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 693643-Chloropropionyl chlorideHCID 78358313Mutated EGFR-IN-12×

Product 1

HCID 866772693-chloro-N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)propanamideYield 97.3%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 887MethanolSolvent

Conditions

Temperature
-20 °C

Procedure

To a stirred suspension of N1-(2-dimethylaminoethyl)-5-methoxy-N1-methyl-N4-[4-(1-methylindol-3-yl)pyrimidin-2-yl]benzene-1,2,4-triamine (Intermediate 175, 33 g, 62.29 mmol) and K2CO3 (6.09 g, 43.6 mmol) in acetone (300 mL) was added 3-chloropropanoyl chloride (9.78 g, 74.74 mmol) at −50° C. The resulting mixture was heated to −20° C. and stirred for 0.5 h. CH3OH (27.75 mL) and NaOH solution (2.24 g, 56.06 mmol in 300 mL water) were added. The resulting mixture was stirred for 3-4 h at r.t. Solid was collected by filtration and dried at 50° C. to give the title compound (32.5 g, 95%). 1H NMR: (CDCl3) 2.95 (2H, t), 3.04 (6H, d), 3.50 (3H, s), 3.63 (2H, s), 3.81 (2H, t), 4.01 (6H, s), 4.33-4.37 (2H, m), 7.33-7.42 (3H, m), 7.47 (1H, t), 7.51-7.55 (1H, m), 8.11-8.21 (3H, m), 8.48 (1H, s), 8.87 (1H, s), 9.17 (1H, s); m/z: ES+ MH+ 536.24.

Workup

  1. stirringThe resulting mixture was stirred for 3-4 h at r.t
  2. filtrationSolid was collected by filtration
  3. customdried at 50° C.

Sources & evidence

ORD record
ord-d6b440462eb649f58ef08047db1c4b22
Source dataset
uspto-grants-2015_02
Patent number
US08946235B2

Reaction notes

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