Chloroform → HCID 59279643, compound

HRID 705173Notes

Reaction equation

HRID 705173 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[N:5]=[CH:4][C:3]=1[CH2:9][NH:10][C:11]1[N:19]=[C:18]([F:20])[N:17]=[C:16]2[C:12]=1[N:13]=[CH:14][NH:15]2.C([O-])([O-])=O.[K+].[K+].Br[CH:28]([CH3:30])[CH3:29].C(Cl)(Cl)Cl>CN(C=O)C.CO>[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[N:5]=[CH:4][C:3]=1[CH2:9][NH:10][C:11]1[N:19]=[C:18]([F:20])[N:17]=[C:16]2[C:12]=1[N:13]=[CH:14][N:15]2[CH:28]([CH3:30])[CH3:29]

Participants

7

Reactant 4

HCID 6212ChloroformHCID 63582-BromopropaneHCID 11430Potassium CarbonateHCID 178425123HCID 178425123, compound

Product 1

HCID 59279643HCID 59279643, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of (4, 6-dimethyl-pyridin-3-ylmethyl)-(2-fluoro-9H-purin-6-yl)-amine (0.6 g, 1.9 mmol) in DMF (10 ml) under an argon atmosphere, at RT, was added K2CO3 (powdered, anhydrous, 1.77 g, 5 eq, 13 mmol) followed by 2-bromopropane (1.8 ml, 10 eq, 19 mmol). The reaction mixture was stirred at RT for 24 h, when TLC (CHCl3: MeOH; 90:10) indicated that the reaction had gone to completion. The solvent was evaporated in vacuo and the residue partitioned between water (50 ml) and ethyl acetate (50 ml), the aqueous phase was separated and extracted with more EtOAc (2×50 ml). The bulked organic phase was washed with brine (50 ml), dried (MgSO4) and evaporated in vacuo, and the residue was purified by gradient column chromatography on silica gel, eluted with CHCl3:MeOH (100:0→95:5), to provide the product as a yellow film (0.4 g, 59%). δH (250 MHz, CDCl3) 1.52 [6 H, d, J 7.5 CH(CH3)2] 2.27 (3 H, s, CH3), 2.45 (3 H, s, CH3), 4.73-4.62 (3 H, m, NHCH2 and CH[CH3]2), 6.91 (1 H, s, ArH), 7.12 (1 H, NH), 7.47 (1 H, s, ArH), 8.32 (1 H, s, ArH); δC (250 MHz, CDCl3) 160.77 (C), 157.89 (C), 157.43 (C), 156.12 (C), 155.79 (C), 149.14 (CH), 137.7 (CH), 128.7 (C), 129.76 (C), 124.83 (CH), 47.2 (CH), 40.14 (CH2), 23.9 (CH3), 22.47 (2×CH3), 18.54 (CH3); m/z 315.3 (M+H)

Workup

  1. customThe solvent was evaporated in vacuo
  2. customthe residue partitioned between water (50 ml) and ethyl acetate (50 ml)
  3. customthe aqueous phase was separated
  4. extractionextracted with more EtOAc (2×50 ml)
  5. washThe bulked organic phase was washed with brine (50 ml)
  6. dry with materialdried (MgSO4)
  7. customevaporated in vacuo
  8. customthe residue was purified by gradient column chromatography on silica gel
  9. washeluted with CHCl3:MeOH (100:0→95:5)
  10. customto provide the product as a yellow film (0.4 g, 59%)

Sources & evidence

ORD record
ord-d0fb432d84e447919d488dde6b3285f7
Source dataset
uspto-grants-2015_11
Patent number
US09173938B2

Reaction notes

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