Dichloromethane → HCID 46831579, compound

HRID 2368785Notes

Reaction equation

HRID 2368785 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:21])=[C:6]([N:8]2[CH:13]=[CH:12][C:11]([C:14]3[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=3)=[N:10][CH:9]2[NH2:20])[CH:7]=1.Cl.[CH3:23][N:24]1[CH2:29][CH2:28][N:27]([C@@H:30]2[C:38]3[C:33](=[CH:34][C:35]([C:39](Cl)=[O:40])=[CH:36][CH:37]=3)[CH2:32][CH2:31]2)[CH2:26][CH2:25]1.[OH-].[Na+].C(Cl)Cl>N1C=CC=CC=1>[CH3:23][N:24]1[CH2:25][CH2:26][N:27]([C@@H:30]2[C:38]3[C:33](=[CH:34][C:35]([C:39]([NH:1][C:2]4[CH:3]=[CH:4][C:5]([CH3:21])=[C:6]([NH:8][C:9]5[N:10]=[C:11]([C:14]6[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=6)[CH:12]=[CH:13][N:20]=5)[CH:7]=4)=[O:40])=[CH:36][CH:37]=3)[CH2:32][CH2:31]2)[CH2:28][CH2:29]1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 14798Sodium HydroxideHCID 67996073HCID 67996073, compoundHCID 86660688HCID 86660688, compound

Product 1

HCID 46831579HCID 46831579, compound

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

N-(5-Amino-2-methylphenyl)-4-(3-pyridyl)-2-aminopyrimidine (681 g, 2.46 mol, 1.1-fold) was dissolved in pyridine (3 L). (1S)-1-(4-Methylpiperazin-1-yl)-2,3-dihydro-1H-indene-5-carbonyl chloride hydrochloride (1325 g, the actual maximum content of 626 g, equivalent to 2.235 mol, 1-fold) was added slowly within 30 minutes with stirring. The solution turned very hot since the reaction was severe but there was no need to have it cool down. After the solution was stirred overnight at room temperature, the reaction solution was added to 2 N aqueous solution of sodium hydroxide (2 L) with stirring, immediately followed by addition of methylene dichloride (2 L). After being stirred for a while, the solution was transferred to a 5 L separatory funnel and then methylene chloride layer was separated. The water phase was extracted with methylene chloride (2×500 mL). The extracts were pooled, dried over anhydrous magnesium sulfate, and then concentrated. The residue was dissolved in methylene dichloride and then purified by silica gel column chromatography using methylene chloride/5% methanol/1% triethylamine as eluent. The fractions containing the desired product were pooled, and concentrated under reduced pressure. The residue was dissolved in 1 L of warm ethyl acetate and crystals were precipitated after stirring. The solid was collected by filtration and dried in vacuum at 50° C. to obtain the title product (617 g, 53% total yield of the three steps). MS (M+1)=520.27.

Workup

  1. temperaturecool down
  2. stirringAfter the solution was stirred overnight at room temperature
  3. stirringwith stirring
  4. stirringAfter being stirred for a while
  5. customthe solution was transferred to a 5 L separatory funnel
  6. custommethylene chloride layer was separated
  7. extractionThe water phase was extracted with methylene chloride (2×500 mL)
  8. dry with materialdried over anhydrous magnesium sulfate
  9. concentrationconcentrated
  10. dissolutionThe residue was dissolved in methylene dichloride
  11. custompurified by silica gel column chromatography
  12. additionThe fractions containing the desired product
  13. concentrationconcentrated under reduced pressure
  14. dissolutionThe residue was dissolved in 1 L of warm ethyl acetate
  15. customcrystals were precipitated
  16. stirringafter stirring
  17. filtrationThe solid was collected by filtration
  18. customdried in vacuum at 50° C.

Sources & evidence

ORD record
ord-f2e754f0b89e4ad4b09fb653a9e5719b
Source dataset
uspto-grants-2014_04
Patent number
US08703771B2

Reaction notes

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