HCID 178491019, compound → HCID 178484166, compound

HRID 511595Notes

Reaction equation

HRID 511595 reaction equation
[C:1]([C:5]1[CH:52]=[CH:51][C:8]2[NH:9][C:10]([CH2:12][CH:13]3[CH2:16][CH:15]([N:17]([CH2:19][C@@H:20]4[C@H:24]5[O:25]C(C)(C)[O:27][C@H:23]5[C@H:22]([N:30]5[C:34]6[N:35]=[CH:36][N:37]=[C:38]([NH:39]CC7C=CC(OC)=CC=7OC)[C:33]=6[CH:32]=[CH:31]5)[O:21]4)[CH3:18])[CH2:14]3)=[N:11][C:7]=2[CH:6]=1)([CH3:4])([CH3:3])[CH3:2]>FC(F)(F)C(O)=O.O>[NH2:39][C:38]1[C:33]2[CH:32]=[CH:31][N:30]([C@H:22]3[C@H:23]([OH:27])[C@H:24]([OH:25])[C@@H:20]([CH2:19][N:17]([CH:15]4[CH2:14][CH:13]([CH2:12][C:10]5[NH:9][C:8]6[CH:51]=[CH:52][C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])=[CH:6][C:7]=6[N:11]=5)[CH2:16]4)[CH3:18])[O:21]3)[C:34]=2[N:35]=[CH:36][N:37]=1

Participants

4

Reactant 1

HCID 178491019HCID 178491019, compound

Product 1

HCID 178484166HCID 178484166, compoundYield 65%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
0 °C

Procedure

7-((3aR,4R,6R,6aR)-6-(((3-((5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)methyl)cyclobutyl)(methyl)amino)methyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)-N-(2,4-dimethoxybenzyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (170 mg, 0.24 mmol) was dissolved in a mixture of trifluoroacetic acid (5.0 mL) and water (0.5 mL) which had been precooled at 0° C. in an ice bath. The solution was stirred at 0° C. for 30 minutes, and warmed to room temperature. After 5 h at room temperature, the now very pink reaction mixture was concentrated. The residue was taken up in 10 mL MeOH and concentrated. This procedure was repeated twice and the residue placed on high vac for 1 h. The material was taken up in 7 mL MeOH and was treated with 130 mg K2CO3 and five 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 a nearly colorless solid. The crude material was purified by flash chromatography (30 g silica gel; 12% 7N NH3 in CH3OH/CH2Cl2) to yield Compound 6 (81 mg, 65%) as a colorless glass/stiff foam: MS (ESI+) for C28H37N7O3 m/z 520.4 (M+H)+; MS (ESI−) for C28H37N7O3 m/z 518.5 (M−H)−; HPLC purity >95% (ret. time, 2.51 min); 1H NMR (400 MHz, d4-MeOH) δH ppm 8.08 (s, 1H), 7.48 (br. s., 1H), 7.39 (d, J=8.50 Hz, 1H), 7.29 (dd, J=8.40, 4.87 Hz, 1H), 6.63 (m, 1H), 6.12 (d, J=4.15 Hz, 1H), 4.40 (m, 1H), 4.09 (m, 2H), 3.15 (m, 0.5H), 3.02 (d, J=8.09 Hz, 1H), 2.92 (d, J=7.26 Hz, 1H), 2.84 (m, 0.5H), 2.65 (m, 2H), 2.43 (m, 1H), 2.29 (m, 1H), 2.20 (d, J=5.80 Hz, 3H), 2.13 (m, 1H), 1.99 (br. s., 1H), 1.67 (m, 1H), 1.37 (d, J=3.94 Hz, 9H), 1.30 (dd, J=13.99, 4.66 Hz, 1H).

Workup

  1. customhad been precooled at 0° C. in an ice bath
  2. temperaturewarmed to room temperature
  3. waitAfter 5 h at room temperature
  4. concentrationthe now very pink reaction mixture was concentrated
  5. concentrationconcentrated
  6. waitthe residue placed on high vac for 1 h
  7. additionwas treated with 130 mg K2CO3 and five drops of water
  8. stirringto stir for 1 hr, during which time the solution
  9. filtrationThe mixture was filtered through a fine frit
  10. washthe solids were washed with 10 mL MeOH
  11. concentrationthe filtrate was concentrated
  12. customto yield a nearly colorless solid
  13. customThe crude material was purified by flash chromatography (30 g silica gel; 12% 7N NH3 in CH3OH/CH2Cl2)

Sources & evidence

ORD record
ord-6edbbdd1f4eb402c8faac709d19b8feb
Source dataset
uspto-grants-2015_08
Patent number
US09096634B2

Reaction notes

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