Tetrahydrofuran → HCID 59605394, compound

HRID 1922996Notes

Reaction equation

HRID 1922996 reaction equation
[CH2:1]([N:3]1[C:11]([CH2:12]O)=[N:10][C:9]2[C:4]1=[N:5][C:6]([N:20]1[C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=3[N:22]=[C:21]1[CH3:29])=[N:7][C:8]=2[N:14]1[CH2:19][CH2:18][O:17][CH2:16][CH2:15]1)[CH3:2].O1CCCC1.P(Br)(Br)[Br:36]>>[Br:36][CH2:12][C:11]1[N:3]([CH2:1][CH3:2])[C:4]2[C:9]([N:10]=1)=[C:8]([N:14]1[CH2:15][CH2:16][O:17][CH2:18][CH2:19]1)[N:7]=[C:6]([N:20]1[C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=3[N:22]=[C:21]1[CH3:29])[N:5]=2

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 24614Phosphorus tribromideHCID 59606188HCID 59606188, compound

Product 1

HCID 59605394HCID 59605394, compoundYield 74.5%

Procedure

To a solution of (9-ethyl-2-(2-methyl-1H-benzo[d]imidazol-1-yl)-6-morpholino-9H-purin-8-yl)methanol (3 g, 7.65 mmol) in tetrahydrofuran (150 mL, 1800 mmol) was added phosphorus tribromide (1.44 mL, 15.3 mmol;) dropwise. The mixture was stirred for 2 hrs until LC/MS showed the reaction was complete. The reaction was quenched with MeOH and extracted with Ethyl acetate and water. The organic layer was collected, dried with Magnesium sulfate, filtered and concentrated to give a crude orange oil. The oil was purified by flash chromatography to give 2.6 g of 4-(8-(bromomethyl)-9-ethyl-2-(2-methyl-1H-benzo[d]imidazol-1-yl)-9H-purin-6-yl)morpholine as an orange solid, of which 50 mg was reacted with 2-(piperidin-4-yl)propan-2-ol via Gen Procedure E to give 34.6 mg 236 following reverse phase purification. MS (Q1) 519.3 (M)+

Workup

  1. customThe reaction was quenched with MeOH
  2. extractionextracted with Ethyl acetate and water
  3. customThe organic layer was collected
  4. dry with materialdried with Magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a crude orange oil
  8. customThe oil was purified by flash chromatography

Sources & evidence

ORD record
ord-45de9170d7b745e29552ab818f679bfe
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

Loading…