Toluene-p-sulphonic anhydride → HCID 178427767, compound

HRID 1028769Notes

Reaction equation

HRID 1028769 reaction equation
[NH2:1][C:2]1[C:3]2[C:10]([C:11]3[CH:20]=[C:19]4[C:14]([CH:15]=[CH:16][C:17]([C:21]5[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=5)=[N:18]4)=[CH:13][CH:12]=3)=[CH:9][N:8]([C@H:27]3[CH2:30][C@H:29]([CH2:31][OH:32])[CH2:28]3)[C:4]=2[N:5]=[CH:6][N:7]=1.[O:33](S(C1C=CC(C)=CC=1)(=O)=O)[S:34]([C:37]1[CH:43]=[CH:42][C:40]([CH3:41])=[CH:39][CH:38]=1)(=O)=[O:35]>C(Cl)Cl.N1C=CC=CC=1.O.C([O-])(O)=O.[Na+]>[NH2:1][C:2]1[C:3]2[C:10]([C:11]3[CH:20]=[C:19]4[C:14]([CH:15]=[CH:16][C:17]([C:21]5[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=5)=[N:18]4)=[CH:13][CH:12]=3)=[CH:9][N:8]([C@H:27]3[CH2:28][C@H:29]([CH2:31][O:32][S:34]([C:37]4[CH:43]=[CH:42][C:40]([CH3:41])=[CH:39][CH:38]=4)(=[O:35])=[O:33])[CH2:30]3)[C:4]=2[N:5]=[CH:6][N:7]=1

Participants

7

Reactant 2

HCID 77773Toluene-p-sulphonic anhydride2×HCID 178508594HCID 178508594, compound

Product 1

HCID 178427767HCID 178427767, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 1049PyridineSolventHCID 6344DichloromethaneSolvent3×HCID 516892Sodium BicarbonateSolvent

Procedure

To a suspension of trans-{3-[4-amino-5-(2-phenylquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclobutyl}-methanol (105.7 mg, 0.251 mmol) in CH2Cl2 (5 mL) and pyridine (1 mL), cooled in a dry ice/acetone bath, was added a solution of Ts2O (92 mg, 0.28 mmol) in CH2Cl2 (2 mL) over 5 min, then the reaction mixture was warmed up to ambient temperature and stirred for 16 h. More Ts2O (70 mg, 0.21 mmol) was added, and stirring at ambient temperature was continued for 4.5 h. The reaction solution was diluted with CH2Cl2 (25 mL), water and saturated NaHCO3 sol. were added, the layers were separated, the aqueous layer was extracted with CH2Cl2 (3×25 mL), and the combined CH2Cl2 extracts were washed with water and brine and dried over MgSO4. Filtration and concentration after adding toluene (10 mL; to remove remaining pyridine as azeotrop) gave the desired product. No purification before the next step. 1H NMR (CDCl3, 400 MHz) δ 2.43-2.51 (m, 2H), 2.47 (s, 2H), 2.67-2.86 (m, 3H), 4.22 (d, J=6.6 Hz, 2H), 5.19 (brs, 2H), 5.36 (quint, J=8.0 Hz, 1H), 7.29 (s, 1H), 7.37-7.41 (m, 2H), 7.46-7.51 (m, 1H), 7.52-7.58 (m, 2H), 7.68 (dd, J=1.8, 8.4 Hz, 1H), 7.83-7.87 (m, 2H), 7.92 (d, J=8.6 Hz, 1H), 7.93 (d, J=8.4 Hz, 1H), 8.17-8.22 (m, 2H), 8.25-8.29 (m, 2H), 8.33 (s, 1H). MS (ES+): m/z 576.1 (54) [MH+], 338.2 (10) [MH+-cyclobutene-CH2OTs]. HPLC: tR=2.8 min (OpenLynx, nonpolar—5 min).

Workup

  1. temperaturecooled in a dry ice/acetone bath
  2. stirringstirring at ambient temperature
  3. waitwas continued for 4.5 h
  4. additionwere added
  5. customthe layers were separated
  6. extractionthe aqueous layer was extracted with CH2Cl2 (3×25 mL)
  7. washthe combined CH2Cl2 extracts were washed with water and brine
  8. dry with materialdried over MgSO4
  9. filtrationFiltration and concentration
  10. additionafter adding toluene (10 mL; to remove remaining pyridine as azeotrop)

Sources & evidence

ORD record
ord-3a96c06062ea446fbb90ec661dfcd02a
Source dataset
uspto-grants-2014_05
Patent number
US08735405B2

Reaction notes

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