Triphenylphosphine → HCID 178501319, compound

HRID 244164Notes

Reaction equation

HRID 244164 reaction equation
[Cl:1][C:2]1[C:3]2[C:10]([I:11])=[CH:9][NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[CH3:12][O:13][C:14]([C@H:16]1[CH2:19][C@@H:18](O)[CH2:17]1)=[O:15].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1>[CH3:12][O:13][C:14]([C@H:16]1[CH2:19][C@H:18]([N:8]2[C:4]3[N:5]=[CH:6][N:7]=[C:2]([Cl:1])[C:3]=3[C:10]([I:11])=[CH:9]2)[CH2:17]1)=[O:15]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 148092816-Chloro-7-iodo-7-deazapurineHCID 178501327HCID 178501327, compound

Product 1

HCID 178501319HCID 178501319, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
75 °C

Procedure

To a mixture of 4-chloro-5-iodo-7H-pyrrolo[2,3-d]pyrimidine (prepared according to: L. B. Townsend et al., J. Med. Chem. 1990, 33 (7), 1984-92) (280 mg, 1.00 mmol), cis-3-hydroxycyclobutanecarboxylic acid methyl ester (trans/cis=1:5) (180 mg, 1.38 mmol), and PS—PPh3 (loading 2.02 mmol/g; 951 mg, 2.02 mmol) in dry THF (10 mL), cooled by ice/water, was added DIAD (295 μL, 303 mg, 1.50 mmol), then the cooling bath was removed, and the mixture was vortexed (220 rpm) for 2 d. The resin was filtered off and washed thoroughly with THF (≈80 mL), the filtrate and washings were combined, concentrated, and chromatographed on silica gel [Jones Flashmaster, 20 g/70 mL cartridge, eluting with CH2Cl2 (1-14)→5% EtOAc in CH2Cl2 (15-30)], fractions containing product were combined and chromatographed again under the same conditions. This material was suspended in iPrOH (≈1.5 mL), heated to 75° C. for 10 min and cooled to −20° C. for 2 h. The solid was filtered off, washed with cold (−20° C.) iPrOH, and dried in vacuo, giving the title compound as white solid, trans/cis=5:1. 1H NMR (CDCl3, 400 MHz) δ 2.83-2.97 (m, 4H), 3.23-3.32 (m, 1H), 3.79 (s, 3H), 5.50 (quint, J=8.7 Hz, 1H), 7.51 (s, 1H), 8.61 (s, 1H). MS (ES+): m/z 391.9/393.9 (100/35) [MH+]. HPLC: tR=3.5 min (OpenLynx, polar—5 min).

Workup

  1. customthe cooling bath was removed
  2. customfor 2 d
  3. filtrationThe resin was filtered off
  4. washwashed thoroughly with THF (≈80 mL)
  5. concentrationconcentrated
  6. customchromatographed on silica gel [Jones Flashmaster, 20 g/70 mL cartridge
  7. washeluting with CH2Cl2 (1-14)→5% EtOAc in CH2Cl2 (15-30)], fractions
  8. additioncontaining product
  9. customchromatographed again under the same conditions
  10. temperaturecooled to −20° C. for 2 h
  11. filtrationThe solid was filtered off
  12. washwashed with cold (−20° C.) iPrOH
  13. customdried in vacuo

Sources & evidence

ORD record
ord-760986b15fee4aeb8b47549db5c98d41
Source dataset
uspto-grants-2014_02
Patent number
US08653268B2

Reaction notes

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