Water → HCID 178457362, compound

HRID 2040685Notes

Reaction equation

HRID 2040685 reaction equation
[CH:1]([N:4]([CH2:25][C@@H:26]1[C@H:30]2[O:31]C(C)(C)[O:33][C@H:29]2[C@H:28]([N:36]2[CH:44]=[N:43][C:42]3[C:37]2=[N:38][CH:39]=[N:40][C:41]=3[NH2:45])[O:27]1)[CH:5]1[CH2:8][CH:7]([CH2:9][CH2:10][C:11]2[NH:15][C:14]3[CH:16]=[CH:17][C:18]([C:20]4([CH3:24])[CH2:23][CH2:22][CH2:21]4)=[CH:19][C:13]=3[N:12]=2)[CH2:6]1)([CH3:3])[CH3:2].FC(F)(F)C(O)=O.O>>[NH2:45][C:41]1[N:40]=[CH:39][N:38]=[C:37]2[C:42]=1[N:43]=[CH:44][N:36]2[C@H:28]1[C@H:29]([OH:33])[C@H:30]([OH:31])[C@@H:26]([CH2:25][N:4]([CH:1]([CH3:3])[CH3:2])[CH:5]2[CH2:6][CH:7]([CH2:9][CH2:10][C:11]3[NH:15][C:14]4[CH:16]=[CH:17][C:18]([C:20]5([CH3:24])[CH2:23][CH2:22][CH2:21]5)=[CH:19][C:13]=4[N:12]=3)[CH2:8]2)[O:27]1

Participants

4

Reactant 3

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 178457360HCID 178457360, compound

Product 1

HCID 178457362HCID 178457362, compoundYield 64.9%

Conditions

Temperature
0 °C

Procedure

9-((3aR,4R,6R,6aR)-6-((isopropyl(3-(2-(5-(1-methylcyclobutyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)amino)methyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)-9H-purin-6-amine 422 mg, 0.686 mmol) was dissolved in a mixture of Trifluoroacetic Acid (6.3 ml, 82 mmol) and water (0.7 ml, 40 mmol) which had been pre-cooled at 0° C. in an ice bath. The solution was stirred at 0° C. for 30 minutes, upon which the ice bath was removed and the mixture was warmed to RT. The mixture was stirred at RT for 2.5 h upon which the residue was taken up in 12 ml MeOH, concentrated to dryness. This was repeated twice, the resultant glass was placed under high vacuum. The crude residue was diluted with 11 ml MeOH, treated with 600 mg K2CO3 and 0.5 ml H2O and allowed to stir at RT till the solution was basic as determined by pH paper. The mixture was filtered and the solids were washed with 20 ml MeOH. The solution was concentrated to a residue that was placed under high vacuum. The crude material was purified by flash chromatography (SiO2, eluting with 10-12% 7N NH3 in CH3OH/CH2Cl2) to give the desired compound as a stiff foam/glass (256 mg). 1H NMR (400 MHz, MeOD) δH ppm 8.30 (m, 1 H), 8.20 (d, J=1.04 Hz, 1 H), 7.38 (d, J=8.09 Hz, 1 H), 7.22 (br. s., 1 H), 6.98 (dd, J=8.50, 1.66 Hz, 1 H), 5.96 (m, 1 H), 4.74 (t, J=4.87 Hz, 1 H), 4.27 (d. J=3.11 Hz, 1 H), 4.08 (m, 1 H), 3.56 (m, 1 H), 3.13 (m, 1 H), 3.00 (m, 1 H), 2.90 (dd, J=14.51, 4.35 Hz, 1 H), 2.75 (m, 3 H), 2.41 (m, 2 H), 2.12 (m, 5 H), 2.00 (m, 1 H), 1.84 (m, 3 H), 1.58 (m, 1 H), 1.46 (s, 3 H), 1.02 (m, 3 H), 0.95 (d, J=6.63 Hz, 3 H).

Workup

  1. customwas removed
  2. temperaturethe mixture was warmed to RT
  3. concentrationconcentrated to dryness
  4. additionThe crude residue was diluted with 11 ml MeOH
  5. additiontreated with 600 mg K2CO3 and 0.5 ml H2O
  6. stirringto stir at RT till the solution
  7. filtrationThe mixture was filtered
  8. washthe solids were washed with 20 ml MeOH
  9. concentrationThe solution was concentrated to a residue that
  10. customThe crude material was purified by flash chromatography (SiO2, eluting with 10-12% 7N NH3 in CH3OH/CH2Cl2)

Sources & evidence

ORD record
ord-d2ed5947af684718b455875dfe8372ed
Source dataset
uspto-grants-2013_11
Patent number
US08580762B2

Reaction notes

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