Pyridine → HCID 178427770, compound

HRID 386243Notes

Reaction equation

HRID 386243 reaction equation
[NH2:1][C:2]1[C:3]2[C:10]([I:11])=[CH:9][N:8]([C@@H:12]3[CH2:15][C@H:14]([CH2:16][OH:17])[CH2:13]3)[C:4]=2[N:5]=[CH:6][N:7]=1.N1C=CC=CC=1.[O:24](S(C1C=CC(C)=CC=1)(=O)=O)[S:25]([C:28]1[CH:34]=[CH:33][C:31]([CH3:32])=[CH:30][CH:29]=1)(=O)=[O:26].C([O-])(O)=O.[Na+]>C(Cl)Cl>[NH2:1][C:2]1[C:3]2[C:10]([I:11])=[CH:9][N:8]([C@@H:12]3[CH2:13][C@H:14]([CH2:16][O:17][S:25]([C:28]4[CH:34]=[CH:33][C:31]([CH3:32])=[CH:30][CH:29]=4)(=[O:26])=[O:24])[CH2:15]3)[C:4]=2[N:5]=[CH:6][N:7]=1

Participants

6

Reactant 4

HCID 1049PyridineHCID 77773Toluene-p-sulphonic anhydrideHCID 516892Sodium BicarbonateHCID 178508628HCID 178508628, compound

Product 1

HCID 178427770HCID 178427770, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Into the suspension of cis-[3-(4-amino-5-iodopyrrolo[2,3-d]pyrimidin-7-yl)-cyclobutyl]-methanol (1322 mg, 3.842 mmol) in CH2Cl2 (55 mL) was added dropwise pyridine (6749 μL, 21.7 eq.) at −78° C. under N2 over 10 min followed by the addition of a solution of Ts2O (1568 mg, 1.25 eq.) in CH2Cl2 (35 mL) over 20 min. After stirring at rt for 3 h, the reaction mixture was treated with saturated NaHCO3, and the organic phase was separated. The aqueous phase was extracted with CH2Cl2 (50 mL). The combined organic phases were washed with H2O (2×100 mL) and brine (100 mL), and dried over MgSO4. After removing the solvent, a brown paste (2050 mg) was obtained. The brown paste was purified by chromatography on silica gel (50 g pre-packed column) and eluted with CH2Cl2 (600 mL), 2% MeOH/CH2Cl2 (600 mL), and 4% MeOH/CH2Cl2 (600 mL) to obtain the title compound as a light-brown foam. 1H NMR (CDCl3, 400 MHz): δ=2.20-2.28 (m, 2 H), 2.47 (s, 3 H), 2.47-2.52 (m, 1 H), 2.57-2.64 (m, 2 H), 4.12-4.13 (d, 2 H, J=5.2 Hz), 5.07-5.11 (m, 1 H), 5.63 (brs, 2 H), 7.14 (s, 1 H), 7.37-7.39 (d, 2 H, J=7.6 Hz), 7.81-7.84 (m, 2 H), 8.22 (s, 1 H). MS (ES+): m/z 498.9 (100) [MH+]. HPLC: tR=3.0 min (OpenLynx, polar—5 min).

Workup

  1. customthe organic phase was separated
  2. extractionThe aqueous phase was extracted with CH2Cl2 (50 mL)
  3. washThe combined organic phases were washed with H2O (2×100 mL) and brine (100 mL)
  4. dry with materialdried over MgSO4
  5. customAfter removing the solvent
  6. customa brown paste (2050 mg) was obtained
  7. customThe brown paste was purified by chromatography on silica gel (50 g pre-packed column)
  8. washeluted with CH2Cl2 (600 mL), 2% MeOH/CH2Cl2 (600 mL), and 4% MeOH/CH2Cl2 (600 mL)

Sources & evidence

ORD record
ord-8336d5b39157496e86bf2b43746d2734
Source dataset
uspto-grants-2013_02
Patent number
US08367826B2

Reaction notes

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