HCID 178491021, compound → HCID 178457186, compound

HRID 2284556Notes

Reaction equation

HRID 2284556 reaction equation
[C:1]([C:5]1[CH:53]=[CH:52][C:8]2[NH:9][C:10]([CH2:12][CH2:13][CH2:14][CH2:15][N:16]([CH2:20][C@@H:21]3[C@H:25]4[O:26]C(C)(C)[O:28][C@H:24]4[C@H:23]([N:31]4[C:35]5[N:36]=[CH:37][N:38]=[C:39]([NH:40]CC6C=CC(OC)=CC=6OC)[C:34]=5[CH:33]=[CH:32]4)[O:22]3)[CH:17]([CH3:19])[CH3:18])=[N:11][C:7]=2[CH:6]=1)([CH3:4])([CH3:3])[CH3:2]>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[C@H:24]([OH:28])[C@H:25]([OH:26])[C@@H:21]([CH2:20][N:16]([CH2:15][CH2:14][CH2:13][CH2:12][C:10]4[NH:9][C:8]5[CH:52]=[CH:53][C:5]([C:1]([CH3:3])([CH3:2])[CH3:4])=[CH:6][C:7]=5[N:11]=4)[CH:17]([CH3:19])[CH3:18])[O:22]3)[C:35]=2[N:36]=[CH:37][N:38]=1

Participants

4

Reactant 1

HCID 178491021HCID 178491021, compound

Product 1

HCID 178457186HCID 178457186, compoundYield 70%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
0 °C

Procedure

7-((3aR,4R,6R,6aR)-6-(((4-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)butyl)(isopropyl)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 (120 mg, 0.16 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 then warmed to room temperature. After 4.5 h at room temperature, the reaction was found to be complete by HPLC and the now 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 6 mL MeOH and was treated with 100 mg K2CO3 and five drops of water. The mixture was stirred for 30 minutes during which time the mixture 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 (20 g silica gel; 8% 7N NH3 in CH3OH/CH2Cl2) to yield the title compound (60 mg, 68%) as a colorless glass: MS (ESI+) for C29H41N7O3 m/z 536.5 (M+H)+; MS (ESI−) for C27H41N7O3 m/z 534.5 (M−H)−; HPLC purity>95% (ret. time, 2.53 min); 1H NMR (400 MHz, d4-MeOH) δ 8.07 (s, 1H), 7.48 (br. s., 1H), 7.38 (d, J=8.50 Hz, 1H), 7.27 (dd, J=8.50, 1.87 Hz, 1H), 7.22 (d, J=3.73 Hz, 1H), 6.61 (d, J=3.73 Hz, 1H), 6.11 (d, J=4.77 Hz, 1H), 4.43 (t, J=5.08 Hz, 1H), 4.14 (t, J=5.49 Hz, 1H), 4.04 (m, 1H), 3.00 (m, 1H), 2.83 (m, 3H), 2.67 (dd, J=14.10, 6.84 Hz, 1H), 2.53 (m, 2H), 1.80 (m, 2H), 1.52 (m, 2H), 1.36 (s, 9H), 1.01 (d, J=6.63 Hz, 3H), 0.97 (d, J=6.63 Hz, 3H).

Workup

  1. customhad been precooled at 0° C. in an ice bath
  2. temperaturewarmed to room temperature
  3. waitAfter 4.5 h at room temperature
  4. concentrationthe now pink reaction mixture was concentrated
  5. concentrationconcentrated
  6. waitthe residue placed on high vac for 1 h
  7. additionwas treated with 100 mg K2CO3 and five drops of water
  8. stirringThe mixture was stirred for 30 minutes during which time the mixture
  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 (20 g silica gel; 8% 7N NH3 in CH3OH/CH2Cl2)

Sources & evidence

ORD record
ord-456ea8e03d1f49ad95ff43e59cf8ea5b
Source dataset
uspto-grants-2015_09
Patent number
US09145438B2

Reaction notes

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