HCID 178491013, compound → HCID 178484137, compound
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]=1Participants
4
Reactant 1
Product 1
Reagents, catalysts & solvents 2
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).