Triphenylphosphine → 7-[(3aS,4R,6R,6aR)-6-(Azidomethyl)-2,2-dimethyl-hexahydrocyclopenta[d][1,3]dioxol-4-yl]-4-chloro-7H-pyrrolo[2,3-d]pyrimidine

HRID 511598Notes

Reaction equation

HRID 511598 reaction equation
[Cl:1][C:2]1[C:3]2[CH:10]=[CH:9][N:8]([C@H:11]3[C@@H:15]4[O:16][C:17]([CH3:20])([CH3:19])[O:18][C@@H:14]4[C@@H:13]([CH2:21]O)[CH2:12]3)[C:4]=2[N:5]=[CH:6][N:7]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O.C1C=CC(OP(OC2C=CC=CC=2)([N:65]=[N+:66]=[N-:67])=O)=CC=1>C1COCC1>[N:65]([CH2:21][C@@H:13]1[C@H:14]2[O:18][C:17]([CH3:19])([CH3:20])[O:16][C@H:15]2[C@H:11]([N:8]2[C:4]3[N:5]=[CH:6][N:7]=[C:2]([Cl:1])[C:3]=3[CH:10]=[CH:9]2)[CH2:12]1)=[N+:66]=[N-:67]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 123414Diphenylphosphoryl azideHCID 76844447((3aR,4R,6R,6aS)-6-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)methanol

Product 1

HCID 866661147-[(3aS,4R,6R,6aR)-6-(Azidomethyl)-2,2-dimethyl-hexahydrocyclopenta[d][1,3]dioxol-4-yl]-4-chloro-7H-pyrrolo[2,3-d]pyrimidineYield 78.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

((3aR,4R,6R,6aS)-6-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)methanol (2.68 g, 8.28 mmol) was dissolved in THF (32 mL), treated with PPh3 (3.05 g, 11.6 mmol), and the reaction vessel was cooled in an ice-brine bath. Diisopropyl azodicarboxylate [DIAD] (2.3 mL, 12 mmol) was added dropwise via syringe and the mixture was stirred for 10 min. A solution of diphenylphosphonic azide [DPPA] (2.50 mL, 11.6 mmol) in THF (7.8 mL) was added dropwise via syringe to afford a off-white mixture, which was stirred for 21 h, allowing the ice bath to warm to RT; HPLC/LC MS indicated complete consumption of starting material and formation of product. At 22.5 h the reaction mixture was concentrated in vacuo and purified by column chromatography (4×22 cm silica; 0-25% EtOAc/Hex) to afford the title compound (2.27 g, 78%) as a clear, colorless oil: MS (ESI+) for C15H17ClN6O2 m/z 349.2 (M+H)+; MS (ESI−) for C15H17ClN6O2 m/z 393.2 (M+HCO2)−; HPLC purity >95% (ret. time, 4.169 min).

Workup

  1. temperaturethe reaction vessel was cooled in an ice-brine bath
  2. customto afford a off-white mixture, which
  3. stirringwas stirred for 21 h
  4. customconsumption of starting material and formation of product
  5. concentrationAt 22.5 h the reaction mixture was concentrated in vacuo
  6. custompurified by column chromatography (4×22 cm silica; 0-25% EtOAc/Hex)

Sources & evidence

ORD record
ord-8c206f0f465a4b8594d1583b1a5c3755
Source dataset
uspto-grants-2015_08
Patent number
US09096634B2

Reaction notes

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