Triphenylphosphine → HCID 178501318, compound

Participants

Reaction Conditions

Reaction Steps

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) (2.10 g, 7.51 mmol), trans-3-hydroxycyclobutanecarboxylic acid methyl ester (trans/cis=5:1) (1.11 g, 8.53 mmol), and PS-PPh3 (loading 2.21 mmol/g; 6.80 g, 15.0 mmol) in dry THF (80 mL), cooled by ice/water, was added DIAD (2.20 mL, 2.26 g, 11.2 mmol), then the cooling bath was removed, and the mixture was vortexed (150 rpm) overnight. The resin was filtered off and washed thoroughly with THF (≈400 mL), the filtrate and washings were combined, concentrated, and chromatographed on silica gel [Jones Flashmaster, 50 g/150 mL cartridge, eluting with CH2Cl2 (1-16)→5% EtOAc in CH2Cl2 (17-40)]. Fractions 3-32 were combined, concentrated, and suspended in iPrOH (10 mL). The suspension was heated to 85° C. for 20 min and cooled to −20° C. for 2 h, the solid was filtered off, washed with cold (−20° C.) iPrOH, and dried in vacuo. One obtained the title compound as white solid. Analytically pure material with cis/trans=50:1 had a melting point of 168-169° C. 1H NMR (CDCl3, 400 MHz): δ=2.66-2.78 (m, 2H), 2.81-2.93 (m, 2H), 3.06 (quint, J=8.7 Hz, 1H), 3.76 (s, 3H), 5.32 (quint, J=8.7 Hz, 1H), 7.68 (s, 1H), 8.60 (s, 1H). 13C NMR (CDCl3, 100.6 MHz, DEPT135): δ=30.93 (+), 34.09 (2C, −), 44.65 (+), 51.58 (Cquart), 52.19 (+), 117.07 (Cquart), 131.87 (+), 150.48 (Cquart), 150.72 (+), 152.69 (Cquart), 174.31 (Cquart). MS (ES+): m/z 391.9/393.9 (100/38) [MH+]. HPLC: tR=3.5 min (OpenLynx, polar—5 min). C12H11ClIN3O2 (391.60): C: calc. 36.81. found 36.88/36.78; H: calc. 2.83. found 2.81/2.76; N: calc. 10.73. found 10.59/10.50.

Provenance & Evidence