HCID 178491013, compound → HCID 178484137, compound

HRID 2040647Notes

Reaction equation

HRID 2040647 reaction equation
[Cl:1][C:2]1[C:3]([C:51]([F:54])([F:53])[F:52])=[CH:4][C:5]2[N:9]=[C:8]([CH2:10][CH2:11][CH:12]3[CH2:15][CH:14]([N:16]([CH2:18][C@@H:19]4[C@H:23]5[O:24]C(C)(C)[O:26][C@H:22]5[C@H:21]([N:29]5[C:33]6[N:34]=[CH:35][N:36]=[C:37]([NH:38]CC7C=CC(OC)=CC=7OC)[C:32]=6[CH:31]=[CH:30]5)[CH2:20]4)[CH3:17])[CH2:13]3)[NH:7][C:6]=2[CH:50]=1>FC(F)(F)C(O)=O.O>[NH2:38][C:37]1[C:32]2[CH:31]=[CH:30][N:29]([C@@H:21]3[CH2:20][C@H:19]([CH2:18][N:16]([CH:14]4[CH2:13][CH:12]([CH2:11][CH2:10][C:8]5[NH:7][C:6]6[CH:50]=[C:2]([Cl:1])[C:3]([C:51]([F:53])([F:52])[F:54])=[CH:4][C:5]=6[N:9]=5)[CH2:15]4)[CH3:17])[C@@H:23]([OH:24])[C@H:22]3[OH:26])[C:33]=2[N:34]=[CH:35][N:36]=1

Participants

4

Reactant 1

HCID 178491013HCID 178491013, compound

Product 1

HCID 178484137HCID 178484137, compoundYield 69%

Reagents, catalysts & solvents 2

HCID 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)(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 (60 mg, 0.078 mmol) was dissolved in a mixture of trifluoroacetic acid (3.6 mL) and water (0.4 mL) which had been precooled at 0° C. in an ice bath. The solution was stirred at 0° C. for 30 minutes, and then warmed to room temperature. After 3 h at room temperature, HPLC indicated the reaction was complete. 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 120 mg K2CO3 and ten drops of water. The mixture was allowed to stir for 1 hr. 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; 10-15% 7N NH3 in CH3OH/CH2Cl2) to yield Compound 7 (31 mg, 69%) as a colorless glass/stiff foam: MS (ESI+) for C27H31ClF3N7O2 m/z 578.3 (M+H)+; MS (ESI−) for C27H31ClF3N7O2 m/z 576.4 (M−H)−; HPLC purity >95% (ret. time, 2.57 min); 1H NMR (400 MHz, d4-MeOD) δH 8.06 (s, 1 H), 7.89 (d, J=2.07 Hz, 1 H), 7.69 (d, J=2.28 Hz, 1 H), 7.21 (dd, J=3.42, 1.76 Hz, 1 H), 6.59 (d, J=3.52 Hz, 1 H), 4.33 (t, J=6.84 Hz, 1 H), 3.89 (q, J=5.25 Hz, 1 H), 3.03 (m, 0.5 H), 2.89 (m, 2 H), 2.70 (m, 0.5 H), 2.49 (m, 1 H), 2.40 (m, 2 H), 2.27 (br. s., 2 H), 2.16 (d, J=7.26 Hz, 4 H), 2.06 (m, 2 H), 1.91 (m, 2 H), 1.62 (m, 1 H), 1.52 (m, 1 H).

Workup

  1. customhad been precooled at 0° C. in an ice bath
  2. temperaturewarmed to room temperature
  3. waitAfter 3 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 120 mg K2CO3 and ten drops of water
  8. stirringto stir for 1 hr
  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; 10-15% 7N NH3 in CH3OH/CH2Cl2)

Sources & evidence

ORD record
ord-20bff4b9a7c042d7b5ed462b6a47475b
Source dataset
uspto-grants-2013_11
Patent number
US08580762B2

Reaction notes

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