Triphenylphosphine → 5-bromo-4-chloro-7-(3-oxetanyl)-7H-pyrrolo[2,3-d]pyrimidine

HRID 1910063Notes

Reaction equation

HRID 1910063 reaction equation
[Br:1][C:2]1[C:10]2[C:5]([NH:6][CH:7]=[N:8][C:9]=2[Cl:11])=[N:4][CH:3]=1.[O:12]1[CH2:15][CH:14](O)[CH2:13]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>O1CCOCC1>[Br:1][C:2]1[C:10]2[C:9]([Cl:11])=[N:8][CH:7]=[N:6][C:5]=2[N:4]([CH:14]2[CH2:15][O:12][CH2:13]2)[CH:3]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 9942117Oxetan-3-olHCID 178478408HCID 178478408, compound

Product 1

HCID 866636865-bromo-4-chloro-7-(3-oxetanyl)-7H-pyrrolo[2,3-d]pyrimidineYield 42.2%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

To 5-bromo-4-chloro-1H-pyrrolo[2,3-d]pyrimidine (300 mg, 1.291 mmol) were added 3-oxetanol (287 mg, 3.87 mmol), polymer bound triphenylphosphine (860 mg, 2.58 mmol) resin and 1,4-Dioxane (2 mL) into a 5 mL microwave vial then DEAD (0.409 mL, 2.58 mmol) was added. The reaction vial was then capped and heated in microwave reactor for 15 minutes at 85° C. The reaction was not complete so it was heated for a total of 1 hr and the reaction was filtered, concentrated, diluted with EtOAc (10 mL) then washed water (10 ml). The water was back extracted with EtOAc (2×10 ml). The organics were combined then washed with brine, dried over MgSO4, filtered and concentrated. The crude was loaded on to a 10 g Biotage column and purified with 0 to 40% EtOAc in Hexane gradient over 30 minutes to afford 5-bromo-4-chloro-7-(3-oxetanyl)-7H-pyrrolo[2,3-d]pyrimidine (157 mg 42.2% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 8.70 (s, 1H), 8.45 (s, 1H), 5.95 (t, J=7.07 Hz, 1H), 4.96-5.04 (m, J=7.07, 7.33, 7.45, 7.45 Hz, 4H).

Workup

  1. customThe reaction vial was then capped
  2. temperaturewas heated for a total of 1 hr
  3. filtrationthe reaction was filtered
  4. concentrationconcentrated
  5. additiondiluted with EtOAc (10 mL)
  6. extractionThe water was back extracted with EtOAc (2×10 ml)
  7. washThe organics were combined then washed with brine
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. custompurified with 0 to 40% EtOAc in Hexane gradient over 30 minutes

Sources & evidence

ORD record
ord-a10a5961bf724cc394908ecfa12e03fe
Source dataset
uspto-grants-2013_12
Patent number
US08598156B2

Reaction notes

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