Water → HCID 58158418, compound

HRID 533216Notes

Reaction equation

HRID 533216 reaction equation
Br[C:2]1[C:6]2[N:7]=[CH:8][N:9]=[C:10]([Cl:11])[C:5]=2[N:4]([CH2:12][O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:3]=1.[Li+].CCC[CH2-].CN([CH:29]=[O:30])C.O>C1(OC)C=CC=CC=1.CCOCC>[CH2:14]([O:13][CH2:12][N:4]1[C:5]2[C:10]([Cl:11])=[N:9][CH:8]=[N:7][C:6]=2[C:2]([CH:29]=[O:30])=[CH:3]1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

7

Reactant 4

HCID 962WaterHCID 6228DimethylformamideHCID 61028n-Butyl lithiumHCID 87240698HCID 87240698, compound

Product 1

HCID 58158418HCID 58158418, compoundYield 57.3%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 7519AnisoleSolvent

Procedure

7-Bromo-5-(benzyloxymethyl)-4-chloro-5H-pyrrolo[3,2-d]pyrimidine (3.73 g, 10.6 mmol) was dissolved in anhydrous anisole (48 ml) and then diluted with Et2O (145 ml) before being cooled to −78° C. at which point N-butyllithium (1.48M in hexane, 9.2 ml, 13.6 mmol) was added dropwise such that the temperature did not exceed −70° C. Within 2 minutes of the addition, DMF (8.5 ml, 0.123 mol) was introduced quickly (T≦−68° and the mixture stirred whilst warming to −40°, at which point water (20 ml) was added. The mixture was then extracted with EtOAc and the extract washed with brine and then dried and concentrated to an orange solid. Purification of this material was accomplished by chromatography over silica, eluting with 20→40% EtOAc/hexane, to give (a heart fraction of) the title aldehyde (1.83 g, 57.3%) as an off-white solid. 1H NMR (CDCl3) δ 10.35 (s, 1H), 8.89 (s, 1H), 8.14 (s, 1H), 7.35-7.20 (m, 5H), 5.90 (s, 2H), 4.60 (s, 2H).

Workup

  1. additionwas added dropwise such that the temperature
  2. customdid not exceed −70° C
  3. additionwas introduced quickly (T≦−68°
  4. additionwas added
  5. extractionThe mixture was then extracted with EtOAc
  6. washthe extract washed with brine
  7. customdried
  8. concentrationconcentrated to an orange solid
  9. customPurification of this material
  10. washeluting with 20→40% EtOAc/hexane

Sources & evidence

ORD record
ord-163670c7c4ae473a8bff2ab0d22810a3
Source dataset
uspto-grants-2014_10
Patent number
US08853224B2

Reaction notes

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