Formaldehyde → HCID 59849184, compound

HRID 604261Notes

Reaction equation

HRID 604261 reaction equation
[Cl:1][C:2]1[C:3]([NH:17][C:18]2[CH:19]=[CH:20][C:21]([N:29]3[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]3)=[C:22]3[C:26]=2[C:25](=[O:27])[N:24]([CH3:28])[CH2:23]3)=[N:4][C:5]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[O:15][CH3:16])=[N:6][CH:7]=1.[CH2:35]=O.[OH-].[Na+]>ClC(Cl)C>[Cl:1][C:2]1[C:3]([NH:17][C:18]2[CH:19]=[CH:20][C:21]([N:29]3[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]3)=[C:22]3[C:26]=2[C:25](=[O:27])[N:24]([CH3:28])[CH2:23]3)=[N:4][C:5]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[O:15][CH3:16])=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 14798Sodium HydroxideHCID 11719940HCID 11719940, compound

Product 1

HCID 59849184HCID 59849184, compoundYield 58.3%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

To a solution of 7-[5-chloro-2-(2-methoxy-phenylamino)-pyrimidin-4-ylamino]-2-methyl-4-piperazin-1-yl-2,3-dihydro-isoindol-1-one (2.0 g, 4.17 mmol) in dichloroethane (50 mL), formaldehyde (380 μL, 5.0 mmol) is added and the mixture is stirred at room temperature for 1.5 hours. After addition of triacetoxy sodium borohydride (1.06 g, 5.0 mmol), the mixture is stirred at room temperature for 1.5 hours. The mixture is poured into 1N sodium hydroxide and stirred at room temperature for 10 min, then extracted twice with dichloromethane. The organic layer is successively washed with water and brine, dried over magnesium sulfate, and evaporated in vacuo. The resulting solids are washed with methanol and ethyl acetate to give 7-[5-Chloro-2-(2-methoxy-phenylamino)-pyrimidin-4-ylamino]-2-methyl-4-(4-methyl-piperazin-1-yl)-2,3-dihydro-isoindol-1-one (1.2 g) as pale yellow solids in 58% yield. Rf=0.30 (MeOH/AcOEt=½). ESI-MS m/z: 494 [MH]+. 1H-NMR (400 MHz, CDCl3, δ, ppm): 2.38 (s, 3H), 2.66-2.57 (m, 4H), 3.09-3.07 (m, 4H), 3.21 (s, 3H), 3.92 (s, 3H), 4.37 (s, 2H), 6.92 (dd, 1H), 7.03-6.96 (m, 2H), 7.13 (d, 1H), 7.45 (s, 1H), 8.11 (s, 1H), 8.33 (dd, 1H), 8.67 (d, 1H), 10.5 (s, 1H).

Workup

  1. stirringthe mixture is stirred at room temperature for 1.5 hours
  2. stirringstirred at room temperature for 10 min
  3. extractionextracted twice with dichloromethane
  4. washThe organic layer is successively washed with water and brine
  5. dry with materialdried over magnesium sulfate
  6. customevaporated in vacuo
  7. washThe resulting solids are washed with methanol and ethyl acetate

Sources & evidence

ORD record
ord-508e572ace404ee8a64525996212a295
Source dataset
uspto-grants-2011_03
Patent number
US07910585B2

Reaction notes

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