2-Bromopropane → (2-Chloro-9-isopropyl-9H-purin-6-yl)-pyridin-3-ylmethyl-amine

HRID 81453Notes

Reaction equation

HRID 81453 reaction equation
[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][NH:8]2)=[C:4]([NH:11][CH2:12][C:13]2[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=2)[N:3]=1.C([O-])([O-])=O.[K+].[K+].Br[CH:26]([CH3:28])[CH3:27]>CN(C=O)C>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH:26]([CH3:28])[CH3:27])=[C:4]([NH:11][CH2:12][C:13]2[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=2)[N:3]=1

Participants

5

Reactant 3

HCID 63582-BromopropaneHCID 11430Potassium CarbonateHCID 178478403HCID 178478403, compound

Product 1

HCID 12112801(2-Chloro-9-isopropyl-9H-purin-6-yl)-pyridin-3-ylmethyl-amineYield 78%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

(2-Chloro-9H-purin-6-yl)-pyridin-3-ylmethyl-amine (110.3 g, 0.37 mol) was dissolved in dry DMF (1.5 L) and warmed to 70° C. with stirring. K2CO3 (230 g, 1.67 mol) and 2-bromopropane (300 mL, 3.20 mol) were added and the reaction was stirred at 70° C. overnight. The reaction mixture was allowed to cool to room temperature and K2CO3 was removed by filtration and washing with EtOAc. The combined filtrate and washings were concentrated on a rotary evaporator and then under high vacuum to remove most of the DMF. The resulting residue was stirred vigorously in H2O (1 L) and CH2Cl2 (1 L) until dissolution was complete. The aqueous layer was extracted with more CH2Cl2 (2×200 mL), the organic extracts were combined, dried over MgSO4, and evaporated to afford the title compound (87.2 g, 78%) as a beige powder. 1H-NMR (DMSO-d6): δ 1.50-1.53 (6H, d, —CH(CH3)2), 4.67-4.72 (3H, m, —CH2—NH— & —CH(CH3)2), 5.20 (1H, br. s, NH), 7.34-7.39 (dd, ArH), 7.76-7.79 (1H, d, ArH), 8.33 (1H, s, ArH, —N═CH—N—), 8.46-8.48 (1H, d, ArH), 8.61 (1H, s, ArH), 8.92 (1H, br. s, NH).

Workup

  1. stirringthe reaction was stirred at 70° C. overnight
  2. temperatureto cool to room temperature
  3. customK2CO3 was removed by filtration
  4. washwashing with EtOAc
  5. concentrationThe combined filtrate and washings were concentrated on a rotary evaporator
  6. customunder high vacuum to remove most of the DMF
  7. stirringThe resulting residue was stirred vigorously in H2O (1 L)
  8. dissolutionCH2Cl2 (1 L) until dissolution
  9. extractionThe aqueous layer was extracted with more CH2Cl2 (2×200 mL)
  10. dry with materialdried over MgSO4
  11. customevaporated

Sources & evidence

ORD record
ord-4665e48385534960bf951e2045b0f7c0
Source dataset
uspto-grants-2014_09
Patent number
US08846696B2

Reaction notes

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