2-Bromopropane → (2-Fluoro-9-isopropyl-9H-purin-6-yl)-pyridin-4-yl-amine

HRID 1432386Notes

Reaction equation

HRID 1432386 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:18]=CN=CC=2)[N:3]=1.C([O-])([O-])=O.[K+].[K+].Br[CH:26]([CH3:28])[CH3:27].C(Cl)(Cl)Cl.CO.[CH3:35][C:36]([N:38](C)C)=O>>[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][C:12]2[CH:13]=[CH:18][N:38]=[CH:36][CH:35]=2)[N:3]=1

Participants

6

Reactant 5

HCID 63582-BromopropaneHCID 11430Potassium CarbonateHCID 31374DimethylacetamideHCID 21584188Chloroform methanolHCID 178506017HCID 178506017, compound

Product 1

HCID 17954000(2-Fluoro-9-isopropyl-9H-purin-6-yl)-pyridin-4-yl-amineYield 57%

Procedure

To a stirred solution of (2-fluoro-9H-purin-6-yl)-pyridin-4-ylmethyl-amine (0.6 g, 2.46 mmol) in DMA (10 mL) under Ar, at RT, was added K2CO3 (powdered, anhydrous, 1.65 g, 11.93 mmol) followed by 2-bromopropane (2.25 mL, 23.96 mmol). The reaction mixture was stirred at RT for 48 h, when TLC (9:1 CHCl3/MeOH) indicated that the reaction had gone to completion. The solvent was evaporated in vacuo and the residue partitioned between H2O (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 (0.40 g, 57%). Mp 270-273° C. 1H-NMR (d6-DMSO, 250 MHz): δ 1.49 (2×s, 6H, —CH(CH3)2), 4.63 (m, 3H, —CH(CH3)2+—HNCH2-Pyr) 7.30, 8.47 (2×m, 4H, Pyr), 8.28 (s, 1H, —N═CH—N—), 8.97 (bs, 1H, —HNCH2-Pyr). FAB-MS 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 H2O (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-6f36094c3b8741fc8915db7e2783c442
Source dataset
uspto-grants-2009_11
Patent number
US07612079B2

Reaction notes

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