Potassium Carbonate → HCID 67775265, compound

HRID 511634Notes

Reaction equation

HRID 511634 reaction equation
[Cl:1][C:2]1[C:50]([Cl:51])=[CH:49][C:5]2[NH:6][C:7]([CH2:9][CH2:10][CH:11]3[CH2:14][CH:13]([N:15]([CH2:17][C@@H:18]4[C@H:22]5[O:23]C(C)(C)[O:25][C@H:21]5[C@H:20]([N:28]5[C:32]6[N:33]=[CH:34][N:35]=[C:36]([NH:37]CC7C=CC(OC)=CC=7OC)[C:31]=6[CH:30]=[CH:29]5)[CH2:19]4)[CH3:16])[CH2:12]3)=[N:8][C:4]=2[CH:3]=1.C([O-])([O-])=O.[K+].[K+]>FC(F)(F)C(O)=O.O>[NH2:37][C:36]1[C:31]2[CH:30]=[CH:29][N:28]([C@@H:20]3[CH2:19][C@H:18]([CH2:17][N:15]([CH:13]4[CH2:12][CH:11]([CH2:10][CH2:9][C:7]5[NH:8][C:4]6[CH:3]=[C:2]([Cl:1])[C:50]([Cl:51])=[CH:49][C:5]=6[N:6]=5)[CH2:14]4)[CH3:16])[C@@H:22]([OH:23])[C@H:21]3[OH:25])[C:32]=2[N:33]=[CH:34][N:35]=1

Participants

5

Reactant 2

HCID 11430Potassium CarbonateHCID 67774686HCID 67774686, compound

Product 1

HCID 67775265HCID 67775265, compoundYield 81.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
0 °C

Procedure

7-((3aS,4R,6R,6aR)-6-(((3-(2-(5,6-Dichloro-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(methyl)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 (377 mg, 0.513 mmol) was dissolved in a mixture of Trifluoroacetic Acid (7.1 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 and stirring was continued for 3 h at RT. The suspension was concentrated and 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 10 ml MeOH (gave a slurry) and was treated with 500 mg K2CO3 and 0.2 ml of water. The mixture was allowed to stir for 1.5 hr, during which time the pH of the solution was −9. The mixture was filtered through a fine frit, the solids were washed with 20 ml MeOH and the filtrate was concentrated to yield an off white solid. The material was left on high vacuum overnight and purified by flash chromatography (SiO2, eluting with 10-12% 7N NH3 in CH3OH/CH2Cl2) to give the desired product (227 mg). 1H NMR (400 MHz, MeOD) δH ppm 8.06 (s, 1H), 7.63 (m, 2H), 7.21 (dd, J=3.63, 2.38 Hz, 1H), 6.59 (d, J=3.52 Hz, 1H), 4.32 (m, 1H), 3.88 (m, 1H), 3.01 (m, 0.5H), 2.84 (m, 2H), 2.70 (m, 0.5H), 2.51 (m, 1H), 2.40 (m, 2H), 2.26 (m, 2H), 2.17 (d, J=7.05 Hz, 3H), 2.11 (m, 2H), 2.02 (m, 1H), 1.90 (m, 3H), 1.62 (m, 1H), 1.49 (m, 1H).

Workup

  1. temperaturewarmed to and
  2. stirringstirring
  3. waitwas continued for 3 h at RT
  4. concentrationThe suspension was concentrated
  5. concentrationconcentrated
  6. customgave a slurry) and
  7. stirringto stir for 1.5 hr, during which time the pH of the solution
  8. filtrationThe mixture was filtered through a fine frit
  9. washthe solids were washed with 20 ml MeOH
  10. concentrationthe filtrate was concentrated
  11. customto yield an off white solid
  12. waitThe material was left on high vacuum overnight
  13. custompurified by flash chromatography (SiO2, eluting with 10-12% 7N NH3 in CH3OH/CH2Cl2)

Sources & evidence

ORD record
ord-4c25228f99e24d3188b7deb4d552dc5e
Source dataset
uspto-grants-2015_08
Patent number
US09096634B2

Reaction notes

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