Potassium Carbonate → HCID 178457356, compound

HRID 511626Notes

Reaction equation

HRID 511626 reaction equation
[Cl:1][C:2]1[C:3]([C:53]([F:56])([F:55])[F:54])=[CH:4][C:5]2[N:9]=[C:8]([CH2:10][CH2:11][CH:12]3[CH2:15][CH:14]([N:16]([CH2:20][C@@H:21]4[C@H:25]5[O:26]C(C)(C)[O:28][C@H:24]5[C@H:23]([N:31]5[C:35]6[N:36]=[CH:37][N:38]=[C:39]([NH:40]CC7C=CC(OC)=CC=7OC)[C:34]=6[CH:33]=[CH:32]5)[CH2:22]4)[CH:17]([CH3:19])[CH3:18])[CH2:13]3)[NH:7][C:6]=2[CH:52]=1.C([O-])([O-])=O.[K+].[K+]>FC(F)(F)C(O)=O.O>[NH2:40][C:39]1[C:34]2[CH:33]=[CH:32][N:31]([C@@H:23]3[CH2:22][C@H:21]([CH2:20][N:16]([CH:14]4[CH2:13][CH:12]([CH2:11][CH2:10][C:8]5[NH:7][C:6]6[CH:52]=[C:2]([Cl:1])[C:3]([C:53]([F:55])([F:54])[F:56])=[CH:4][C:5]=6[N:9]=5)[CH2:15]4)[CH:17]([CH3:19])[CH3:18])[C@@H:25]([OH:26])[C@H:24]3[OH:28])[C:35]=2[N:36]=[CH:37][N:38]=1

Participants

6

Reactant 2

HCID 11430Potassium CarbonateHCID 178491016HCID 178491016, compound

Product 1

HCID 178457356HCID 178457356, compound

Reagents, catalysts & solvents 3

HCID 962WaterCatalystHCID 962WaterSolventHCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
0 °C

Procedure

7-((3aS,4R,6R,6aR)-6-(((3-(2-(6-chloro-5-(trifluoromethyl)-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 (525 mg, 0.683 mmol) was dissolved in a mixture of Trifluoroacetic Acid (9 ml) and Water (1 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 4 h at RT, the mixture was concentrated. The residue was taken up in 20 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 15 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 fine frit, 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 12% 7N NH3 in CH3OH/CH2Cl2) to give a colorless glass/stiff foam. 1H NMR (400 MHz, MeOD) δH ppm 8.06 (s, 1H), 7.89 (d, J=2.07 Hz, 1H), 7.69 (d, J=2.28 Hz, 1H), 7.21 (dd, J=3.42, 1.76 Hz, 1H), 6.59 (d, J=3.52 Hz, 1H), 4.33 (t, J=6.84 Hz, 1H), 3.89 (q, J=5.25 Hz, 1H), 3.03 (m, 0.5H), 2.89 (m, 2H), 2.70 (m, 0.5H), 2.49 (m, 1H), 2.40 (m, 2H), 2.27 (br. s., 2H), 2.16 (d, J=7.26 Hz, 4H), 2.06 (m, 2H), 1.91 (m, 2H), 1.62 (m, 1H), 1.52 (m, 1H).

Workup

  1. temperaturewarmed to RT
  2. waitAfter 4 h at RT
  3. concentrationthe mixture was concentrated
  4. concentrationconcentrated
  5. customgave a slurry) and
  6. stirringto stir for 1 hr, during which time the solution
  7. filtrationThe mixture was filtered through a fine frit
  8. washthe solids were washed with 10 ml MeOH
  9. concentrationthe filtrate was concentrated
  10. customto yield an off white solid
  11. waitThe material was left on high vacuum overnight
  12. customThe crude material was purified by flash chromatography (SiO2, eluting with 12% 7N NH3 in CH3OH/CH2Cl2)
  13. customto give a colorless glass/stiff foam

Sources & evidence

ORD record
ord-24fbdccb271048e9acb7bb6f947da920
Source dataset
uspto-grants-2015_08
Patent number
US09096634B2

Reaction notes

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