Potassium Carbonate → HCID 178457355, compound

HRID 511625Notes

Reaction equation

HRID 511625 reaction equation
[C:1]([C:5]1[CH:55]=[CH:54][C:8]2[NH:9][C:10]([CH2:12][CH2:13][CH:14]3[CH2:17][CH:16]([N:18]([CH2:22][C@@H:23]4[C@H:27]5[O:28]C(C)(C)[O:30][C@H:26]5[C@H:25]([N:33]5[C:37]6[N:38]=[CH:39][N:40]=[C:41]([NH:42]CC7C=CC(OC)=CC=7OC)[C:36]=6[CH:35]=[CH:34]5)[CH2:24]4)[CH:19]([CH3:21])[CH3:20])[CH2:15]3)=[N:11][C:7]=2[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[K+].[K+]>FC(F)(F)C(O)=O.O.CO>[NH2:42][C:41]1[C:36]2[CH:35]=[CH:34][N:33]([C@@H:25]3[CH2:24][C@H:23]([CH2:22][N:18]([CH:16]4[CH2:15][CH:14]([CH2:13][CH2:12][C:10]5[NH:9][C:8]6[CH:54]=[CH:55][C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])=[CH:6][C:7]=6[N:11]=5)[CH2:17]4)[CH:19]([CH3:20])[CH3:21])[C@@H:27]([OH:28])[C@H:26]3[OH:30])[C:37]=2[N:38]=[CH:39][N:40]=1

Participants

7

Reactant 2

HCID 11430Potassium CarbonateHCID 178491015HCID 178491015, compound

Product 1

HCID 178457355HCID 178457355, compoundYield 75.6%

Reagents, catalysts & solvents 4

HCID 962WaterCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
0 °C

Procedure

7-((3aS,4R,6R,6aR)-6-(((3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-N-(2,4-dimethoxybenzyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (390 mg, 0.52 mmol) was dissolved in a mixture of Trifluoroacetic Acid (7.2 ml) and Water (0.8 ml) which had been pre-cooled at 0° C. in an ice bath. The solution was stirred at 0° C. for 30 minutes, then warmed to RT After 2.5 at RT the residue was taken up in 15 ml MeOH and concentrated. This procedure was repeated twice and the residue placed on high vacuum. The material was taken up in 15 ml MeOH (gave a slurry) and was treated with 500 mg K2CO3 and 8 drops of water. The mixture was allowed to stir for 1 hr, during which time the solution was found to be basic. The mixture was filtered through a finefrit, the solids were washed with 10 ml MeOH and the filtrate was concentrated to yield an off white solid. The material was left on high vacuum overnight. The crude material was purified by flash chromatography (SiO2, eluting with 8-10% 7N NH3 in CH3OH/CH2Cl2) to give a glass/stiff foam (0.22 g). 1H NMR (400 MHz, MeOD) δH ppm 8.06 (s, 1H), 7.48 (br. s., 1H), 7.39 (m, 1H), 7.27 (m, 1H), 7.20 (d, J=3.52 Hz, 1H), 6.60 (m, 1H), 4.32 (t, J=6.43 Hz, 1H), 3.93 (t, J=5.29 Hz, 1H), 3.54 (m, 0.2H), 3.11 (t, J=9.33 Hz, 1H), 3.02 (m, 1H), 2.82 (m, 2H), 2.66 (dd, J=13.68, 8.09 Hz, 1H), 2.46 (m, 1H), 2.36 (m, 1H), 2.23 (m, 3H), 2.05 (m, 1H), 1.91 (m, 3H), 1.59 (m, 3H), 1.36 (s, 9H), 1.02 (m, 6H).

Workup

  1. temperaturewarmed to RT After 2.5 at RT the residue
  2. concentrationconcentrated
  3. customgave a slurry) and
  4. stirringto stir for 1 hr, during which time the solution
  5. filtrationThe mixture was filtered through a finefrit
  6. washthe solids were washed with 10 ml MeOH
  7. concentrationthe filtrate was concentrated
  8. customto yield an off white solid
  9. waitThe material was left on high vacuum overnight
  10. customThe crude material was purified by flash chromatography (SiO2, eluting with 8-10% 7N NH3 in CH3OH/CH2Cl2)

Sources & evidence

ORD record
ord-b9a29189a78441e5833a8cbf2faf04ae
Source dataset
uspto-grants-2015_08
Patent number
US09096634B2

Reaction notes

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