Water → HCID 178484134, compound

HRID 511648Notes

Reaction equation

HRID 511648 reaction equation
COC1C=C(OC)C=CC=1C[NH:6][C:7]1[C:8]2[CH:15]=[CH:14][N:13]([C@H:16]3[C@H:23]4[C@H:19]([O:20]C(C)(C)[O:22]4)[C@@H:18]([CH2:26][N:27]([CH3:48])[CH:28]4[CH2:31][CH:30]([CH2:32][CH2:33][C:34]5[NH:38][C:37]6[CH:39]=[CH:40][C:41]([C:43]7([CH3:47])[CH2:46][CH2:45][CH2:44]7)=[CH:42][C:36]=6[N:35]=5)[CH2:29]4)[CH2:17]3)[C:9]=2[N:10]=[CH:11][N:12]=1.FC(F)(F)C(O)=O.O.C([O-])([O-])=O.[K+].[K+]>CO.O>[NH2:6][C:7]1[C:8]2[CH:15]=[CH:14][N:13]([C@@H:16]3[CH2:17][C@H:18]([CH2:26][N:27]([CH3:48])[CH:28]4[CH2:29][CH:30]([CH2:32][CH2:33][C:34]5[NH:38][C:37]6[CH:39]=[CH:40][C:41]([C:43]7([CH3:47])[CH2:44][CH2:45][CH2:46]7)=[CH:42][C:36]=6[N:35]=5)[CH2:31]4)[C@@H:19]([OH:20])[C@H:23]3[OH:22])[C:9]=2[N:10]=[CH:11][N:12]=1

Participants

7

Reactant 4

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 178491009HCID 178491009, compound

Product 1

HCID 178484134HCID 178484134, compoundYield 3.1%

Reagents, catalysts & solvents 2

HCID 962WaterCatalystHCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

N-(2,4-dimethoxybenzyl)-7-((3aS,4R,6R,6aR)-2,2-dimethyl-6-((methyl(3-(2-(5-(1-methylcyclobutyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)amino)methyl)tetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (128 mg, 0.17 4 mmol) was dissolved in a mixture of Trifluoroacetic Acid (3.60 ml, 46.7 mmol) and Water (0.4 ml, 20 mmol) which had been pre-cooled at 0° C. in an ice bath. The solution was stirred at 0° C. for 30 minutes, then the ice bath was removed and the mixture was warmed to RT at which this temperature was maintained for a further 2.5 hours. The reaction mixture was concentrated in vacuo. The residue was taken up in 3 ml MeOH and concentrated and the process was repeated twice. The resultant white residue was placed on high vacuum. The crude residue was combined with another batch of crude material (prepared identically, ˜⅓ of the amount used in this reaction), diluted with 5 mL MeOH, treated with 140 mg K2CO3, 10 drops of H2O and allowed to stir at RT till the solution was basic by pH paper. The mixture was filtered and the solids were washed with 15 ml MeOH. The solution was concentrated to an oil that was placed on high vacuum. The crude material was purified by flash chromatography (SiO2, eluting with 10-15% 7N NH3 in CH3OH/CH2Cl2 to yield the desired product as glass/stiff foam (68 mg). 1H NMR (400 MHz, MeOD) δH ppm 8 06 (s, 1H), 7.39 (d, J=7.88 Hz, 1H), 7.23 (s, 1H), 7.21 (dd, J=3.63, 1.76 Hz, 1H), 6.99 (m, 1H), 6.60 (d, J=3.52 Hz, 1H), 4.93 (m, 1H), 4.32 (m, 1H), 3.89 (m, 1H), 3.03 (m, 1H), 2.83 (m, 2H), 2.70 (q, J=8.15 Hz, 1H), 2.52 (m, 1H), 2.40 (m, 4H), 2.27 (m, 2H), 2.18 (d, J=6.22 Hz, 3H), 2.11 (m, 4H), 2.03 (m, 1H), 1.86 (m, 4H), 1.62 (m, 1H), 1.51 (m, 1H), 1.47 (s, 3H).

Workup

  1. customthe ice bath was removed
  2. temperaturethe mixture was warmed to RT at which this temperature
  3. temperaturewas maintained for a further 2.5 hours
  4. concentrationThe reaction mixture was concentrated in vacuo
  5. concentrationconcentrated
  6. customprepared identically
  7. custom˜⅓ of the amount used in this reaction),
  8. stirringto stir at RT till the solution
  9. filtrationThe mixture was filtered
  10. washthe solids were washed with 15 ml MeOH
  11. concentrationThe solution was concentrated to an oil that
  12. customThe crude material was purified by flash chromatography (SiO2
  13. washeluting with 10-15% 7N NH3 in CH3OH/CH2Cl2

Sources & evidence

ORD record
ord-ab713fbe03a34f7e943cc1e47d3895ba
Source dataset
uspto-grants-2015_08
Patent number
US09096634B2

Reaction notes

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