Chloroform → 2-fluoro-9-isopropyl-N-(pyridin-3-ylmethyl)-9H-purin-6-amine

HRID 729581Notes

Reaction equation

HRID 729581 reaction equation
[F: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].C(Cl)(Cl)Cl>CC(N(C)C)=O.CO>[F: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

7

Reactant 4

HCID 6212ChloroformHCID 63582-BromopropaneHCID 11430Potassium CarbonateHCID 178506016HCID 178506016, compound

Product 1

HCID 115220602-fluoro-9-isopropyl-N-(pyridin-3-ylmethyl)-9H-purin-6-amine

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 31374DimethylacetamideSolvent

Procedure

To a stirred solution of (2-fluoro-9H-purin-6-yl)-pyridin-3-ylmethyl-amine (1.00 g, 1 eq, 4.10 mmol) in DMA (12 mL) under an argon atmosphere, at RT, was added K2CO3 (powdered, anhydrous, 2.75 g, 4.85 eq, 19.90 mmol) followed 2-bromopropane (3.75 mL, 9.75 eq, 39.93 mmol). The reaction mixture was stirred at RT for 48 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 (200 mL) and EtOAc (100 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 afford the title compound as a white solid. Yield: 0.73 g (62%). Mp 131-133° C. 1H-NMR (d6-DMSO, 250 MHz): δ1.49 (2×s, 6H, —CH(CH3)2), 4.63 (m, 3H, —CH(CH3)2 & —HNCH2-Pyr), 7.34, 7.24, 8.44, 8.58 (4×m, 4H, Pyr), 8.26 (s, 1H, —N═CH—N—), 8.95 (bs, 1H, —HNCH2-Pyr). FABMS m/z (relative intensity): 287 ([M+H]+, 100), 245 (8), 154 (23), 136 (18). Accurate Mass (M+H): Actual: 287.1420, Measured: 287.1412. Microanalysis (Expected: Measured) C14H15N6F: C, 58.73; 58.57; H, 5.28; 5.21; N, 29.35; 29.27.

Workup

  1. customThe solvent was evaporated in vacuo
  2. customthe residue partitioned between water (200 mL) and EtOAc (100 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)

Sources & evidence

ORD record
ord-f6c9ae14ebce4cadb6eb81e09bdeb5ce
Source dataset
uspto-grants-2009_09
Patent number
US07582642B2

Reaction notes

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